Showing papers in "Hypertension in 1987"

Fructose-induced insulin resistance and hypertension in rats.

Abstract: To determine if hypertension could be produced in normal rats by feeding them a fructose-enriched diet, Sprague-Dawley rats were fed either normal chow or a diet containing 66% fructose as a percentage of total calories for approximately 2 weeks. At the end of this period systolic blood pressure had increased from 124 +/- 2 to 145 +/- 2 (SEM) mm Hg in the fructose-fed rats, whereas no change occurred in the control group. In addition, hyperinsulinemia and hypertriglyceridemia were associated with hypertension in fructose-fed rats. The addition of clonidine to the drinking water inhibited fructose-induced hypertension, but not the increase in plasma insulin or triglyceride concentration seen in fructose-fed rats. Thus, the metabolic changes associated with fructose-induced hypertension are unlikely to be secondary to an increase in sympathetic activity. Whether or not this is also true of the hypertension remains to be clarified.

Assessment of baroreceptor reflex sensitivity by means of spectral analysis.

Abstract: A method of determining baroreceptor reflex sensitivity is proposed that is based on spectral analysis of systolic pressure values and RR interval times, namely, the modulus (or gain) in the mid frequency band (0.07-0.14 Hz) between these two signals. Results using this method were highly correlated (0.94; n = 8) with results of the phenylephrine method. In addition, compared with the values for the preceding rest period, the modulus decreased during mental challenge, as might be expected from the literature.

Detection of Left Ventricular Hypertrophy by M-Mode Echocardiography Anatomic Validation, Standardization, and Comparison to Other Methods

Abstract: Because of its simplicity, widespread availability, relatively low cost, and lack of adverse effects, M-mode echocardiography has become the most widely used technique for measurement of human left ventricular mass. Necropsy comparison studies have yielded formulas for anatomically accurate estimation of left ventricular mass in patients with normally shaped ventricles using left ventricular measurements by either Penn or American Society of Echocardiography conventions, but M-mode methods are less accurate in abnormally shaped ventricles. The standard error of M-mode echocardiographic left ventricular mass measurements is approximately 40 g under difficult clinical recording conditions and 30 g or less for research studies of stable subjects. Interstudy variability of mass estimates appeared somewhat lower, resulting in 95% confidence limits for serial change up to 58 g for individual subjects and up to 10 g for study populations of 34 patients or more. The accuracy of M-mode echocardiography for measurement of left ventricular mass is similar to that of contrast angiography but may be exceeded by newer methods with greater cost or radiation exposure, including magnetic resonance imaging, cine-computed tomography, and three-dimensional echocardiographic reconstruction. Identification of left ventricular hypertrophy needs to take into account the influence of sex and body size, the variables that most influence normal ventricular mass, with provisional criteria for recognition of hypertrophy being left ventricular mass index over 134 g/m2 in men and above 110 g/m2 in women.

Effects of the cold pressor test on muscle sympathetic nerve activity in humans.

Abstract: The purpose of this study was to determine the effects of the cold pressor test on sympathetic outflow with direct measurements of nerve traffic in conscious humans and to test the strength of correlation between sympathetic nerve discharge and the changes in arterial pressure, heart rate, and plasma norepinephrine. In 25 healthy subjects, arterial pressure, heart rate, and muscle sympathetic nerve activity were measured with microelectrodes inserted percutaneously into a peroneal muscle nerve fascicle in the leg during immersion of the hand in ice water for 2 minutes. Arterial pressure rose steadily during the first and second minutes of the cold pressor test. Muscle sympathetic activity (burst frequency X amplitude) did not increase in the first 30 seconds of the test but increased from 230 +/- 27 to 386 +/- 52 units (mean +/- SE, p less than 0.05) by the end of the first minute of the test and to 574 +/- 73 (p less than 0.01) during the second minute. In contrast, heart rate increased maximally during the first 30 seconds of the cold pressor test and returned to control during the second minute. The increases in heart rate were abolished by beta-adrenergic blockade. The increases in muscle sympathetic activity during the cold pressor test were correlated with the increases in both mean arterial pressure (r = 0.86, p less than 0.01) and peripheral venous norepinephrine (r = 0.72, p less than 0.05); however, large changes in nerve traffic were associated with small changes in plasma norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Alerting reaction and rise in blood pressure during measurement by physician and nurse.

Abstract: Blood pressure was monitored by a continuous intra-arterial recording in 46 subjects to investigate whether the alarm reaction and the blood pressure and heart rate increases that occur during cuff blood pressure measurement made by a physician 1) attenuate when the physician's visit is repeated several times and 2) are less pronounced if a nurse measures the blood pressure. In 16 subjects the peak mean blood pressure and heart rate rises that occurred in the early part of the physician's first visit (22.6 +/- 1.8 mm Hg and 17.7 +/- 1.7 beats/min) were virtually identical to those occurring during three subsequent visits by the same physician throughout a 2-day intra-arterial blood pressure monitoring. The less pronounced pressor and tachycardic responses observed in the last part of the physician's visit also were virtually identical among the four visits. In contrast, in 30 other subjects the blood pressure and heart rate rises that occurred during the nurse's visit were 46.7% and 42.1% less (p less than 0.01) than those occurring during the physician's visit. The late and less pronounced pressor and tachycardic responses to the visit were also significantly less (p less than 0.01) in the former than in the latter condition. These results indicate that the error of overestimation of blood pressure inherent in cuff blood pressure measurement by a physician cannot be avoided by repeated visits by the physician over a short time span. It clearly can be reduced, however, if blood pressure measurements are performed by a nurse.

Endothelium-dependent vascular responses in normotensive and hypertensive Dahl rats.

Abstract: Experiments were designed to study endothelium-dependent responses in salt-sensitive (DS) and salt-resistant Dahl rats (DR). The rats were fed a low sodium (0.1% NaCl) or high sodium (8% NaCl) diet for 8 weeks. Blood pressure in DS fed a high sodium diet was higher than that in the remaining animals. Aortic rings with and without endothelium were suspended for isometric tension recording. Acetylcholine, adenosine 5'-diphosphate, and thrombin induced endothelium-dependent relaxations that were significantly depressed in the aorta of DS fed a high sodium diet. The relaxations in response to sodium nitroprusside were only slightly, but significantly, depressed in DS fed a high sodium diet. Removal of the endothelium greatly enhanced the response to serotonin and norepinephrine. In rings with, but not without, endothelium taken from rats fed a high sodium diet, the tension developed in response to serotonin and norepinephrine was significantly greater than that in animals fed a low sodium diet. These experiments indicate that endothelium-dependent relaxations to acetylcholine, adenosine 5'-diphosphate, and thrombin are depressed in hypertensive Dahl rats; this effect probably reflects a decreased release of endothelium-derived relaxing factor(s), although structural changes might contribute; and the responsiveness to vasoconstrictor agents is increased in DS and DR fed a high sodium diet. These findings may indicate differential effects of blood pressure and dietary salt on endothelial function.

Alcohol consumption and hypertension.

Abstract: An increased prevalence of hypertension in groups with high alcohol consumption has been recognized for a number of years. More recently, several studies have suggested an independent association between alcohol consumption and blood pressure levels in samples from general populations. Of 30 cross-sectional population studies reviewed, the majority reported small but significant elevations in blood pressure in those consuming three drinks or more per day in comparison with nondrinkers. In 25% of studies, elevations in blood pressure were also reported at lower levels of consumption; in about 40%, the blood pressure of nondrinkers was greater than that of those consuming one to two drinks per day. In two studies, one from the United States and one from Australia, the maximum contribution to the prevalence of hypertension of alcohol consumption greater than two drinks per day was estimated to be 5 to 7%; the contribution in men (11%) was greater than that in women because of their greater alcohol consumption. A prospective association of alcohol consumption with change in blood pressure was observed in five studies. In a small number of experimental studies, short-term falls in blood pressure accompanied alcohol restriction in both normotensive and hypertensive subjects. Uncontrolled observations in heavy drinking populations suggest that the effect on blood pressure of alcohol withdrawal may be lasting. However, firm conclusions about the long-term effects of alcohol restriction, particularly in moderate consumers who represent a large proportion in many populations, must await long-term controlled trials.

Influence of blood pressure on development of aortic medial smooth muscle hypertrophy in spontaneously hypertensive rats.

Abstract: The hypothesis that a primary stimulus for aortic medial hypertrophy in spontaneously hypertensive rats (SHR) is increased blood pressure was tested by determining whether development of smooth muscle cell hypertrophy and hyperploidy in SHR could be dissociated from blood pressure levels in rats treated with various antihypertensive drugs with different mechanisms of action. Wistar-Kyoto rats (WKY) and SHR were treated between 2 and 5 months of age with captopril (375 mg/L), hydralazine (40 mg/L), or propranolol (1.5 mg/L) administered in their drinking water. Smooth muscle hypertrophy and hyperploidy were analyzed by morphometric evaluation of medial smooth muscle content, flow cytometric analysis of the frequency of polyploid smooth muscle cells, and biochemical estimates of smooth muscle cell number. All drugs significantly lowered blood pressure in SHR compared with untreated controls (order of efficacy: captopril greater than hydralazine greater than propranolol). Captopril also was most effective at changing blood pressure in WKY, while propranolol and hydralazine had similar blood pressure-lowering effects. The efficacy of drugs in preventing the development of smooth muscle cell polyploidism and medial hypertrophy in SHR was the same as their efficacy in lowering blood pressure, although propranolol had no effect on medial smooth muscle hypertrophy despite lowering blood pressure by 26 mm Hg. Regression analyses showed a high degree of correlation between blood pressure and the frequency of polyploid smooth muscle cells and medial smooth muscle content. These results are consistent with the hypothesis that aortic medial hypertrophy may be, in part, a response to increased blood pressure or wall stress. However, analysis of covariance and two-stage multiple regression analyses indicated that captopril had an effect over and above that predicted by its blood pressure-lowering effect. Furthermore, propranolol lowered blood pressure but did not affect medial hypertrophy. These results suggest that smooth muscle hypertrophy is not simply a response to increased blood pressure, but that other factors, such as angiotensin II, may be important in modulating aortic medial hypertrophy in SHR.

Renal function curve--a key to understanding the pathogenesis of hypertension.

Abstract: I N this issue of Hypertension is an article by Kimura and his colleagues 1 entitled \"Renal Function Curve in Patients with Secondary Forms of Hypertension.\" When I was asked to write a comment on this article, I first thought that it might not be useful because the article itself is quite clear. Yet, for very subtle reasons, considerable confusion does remain about the importance and utility of renal function curves in understanding the pathophysiology of hypertension. This is true partly because there are several different types of renal function curves, and each has a slightly different significance, as I shall explain. Historically, my own interest in renal function curves as a tool for understanding hypertensive mechanisms dates back to the mid-1960s, when Dr. Thomas Coleman and I were first developing computer models of arterial pressure regulation and hyper-tensive mechanisms. At one step in a model we used a renal function curve that depicted the effect of arterial pressure on urinary output. In running the model, we were quite surprised to see that so long as the renal function curve remained immutable and the rate of salt and water intake also remained constant changing any other variable in the model did not change the predicted level to which the arterial pressure was regulated. 2 Among the changes that did not alter the predicted pressure level were 1) changes in heart strength, 2) changes in total peripheral resistance, and 3) changes in vascular compliance. The reader will recognize these hemodynamic variables as the ones most often invoked in various explanations of hypertension. Therefore, at first, we were greatly surprised to see the predictions. Yet, within seconds, we were able to trace through the model and understand exactly why the final predicted level of arterial pressure was always the same so long as the renal function curve and the rate of intake remained constant. Let me first discuss this result of the computer model; then I will attempt to explain its applicability both to the article by Kimura et al. 1 and to the general principles of arterial pressure regulation and hypertension. The essence of the computer model that Dr. Coleman and I used for understanding arterial pressure regulation as well as many types of hypertension is summarized in the simple diagram shown in Figure 1. This figure illustrates one type of renal function curve, the type that plots the urinary sodium …

Dissociation of sympathetic nerve activity in arm and leg muscle during mental stress.

Abstract: Mental stress, which increases blood pressure and heart rate, increases forearm blood flow but does not change calf blood flow. The purpose of this study was to determine if mental stress increases muscle sympathetic nerve activity in the leg and causes a dissociation of muscle sympathetic nerve activity in the arm and the leg. We recorded heart rate, blood pressure, and efferent sympathetic nerve activity during mental stress (4 minutes of mental arithmetic) in 13 healthy men. Microelectrodes were inserted percutaneously into a fascicle of the peroneal nerve (leg) and radial nerve (arm) to measure sympathetic discharge to muscle. In Study 1, leg muscle sympathetic nerve activity was recorded in seven subjects. Mental stress significantly increased heart rate and blood pressure. Despite the increased blood pressure (which would be expected reflexly to inhibit sympathetic nerve activity), leg muscle sympathetic nerve activity (in total integrated activity, bursts per 100 heart beats or bursts per minute) increased significantly during stress. Further, whereas heart rate and blood pressure returned to normal during recovery, leg muscle sympathetic nerve activity remained elevated during recovery. In Study 2, simultaneous recordings were made of arm and leg muscle sympathetic nerve activity in six subjects. Mental stress increased heart rate and arterial pressure. Leg muscle sympathetic nerve activity again increased significantly during stress and remained elevated during recovery. In contrast, arm muscle sympathetic nerve activity did not change during stress. However, arm muscle sympathetic nerve activity increased significantly during recovery after stress. These studies indicate that a sympathoexcitatory influence of mental stress overrides or inhibits baroreceptor control of leg sympathetic nerve activity and stress causes a dissociation of arm and leg muscle sympathetic nerve activity with increased outflow to the leg but not to the arm. These observations may contribute to differences in blood flow to arm and leg during mental stress.

Antihypertensive and volume-depleting effects of mild exercise on essential hypertension.

Abstract: After a general clinical observation period of over 4 weeks, 20 essential hypertensive subjects (Japanese) were randomly divided into two groups. One group (n = 10; 4 men and 6 women; 51.4 +/- 2.8 years of age) agreed to physical training using bicycle ergometer exercise with the intensity at blood lactate threshold for 60 minutes three times a week for 10 weeks, while the other group (n = 10; 4 men and 6 women; 51.0 +/- 2.9 years of age) did no particular physical training and was followed once a week as the control. Changes in blood pressure, hemodynamics, and humoral factors of the exercised group were compared with values in the controls. The following significant changes were found only in the exercised group. Blood pressure was significantly (p less than 0.01) reduced. Whole blood and plasma volume indices were significantly reduced (p less than 0.05, p less than 0.01, respectively). The change in ratio of serum sodium to potassium positively correlated with the change in systolic blood pressure (r = 0.76, p less than 0.02). Plasma norepinephrine concentrations both at rest and at the workload of blood lactate threshold during graded exercise tests were significantly reduced (p less than 0.05, p less than 0.02 respectively) after 10 weeks of exercise training. The change in the resting level of plasma norepinephrine positively correlated with that in the mean blood pressure. No such changes were observed in the control group. In both groups, body weight and urinary sodium excretion showed no statistically significant changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive treatment normalizes decreased endothelium-dependent relaxations in rats with salt-induced hypertension.

Abstract: Endothelium-dependent responses are impaired in various models of hypertension. The effects of antihypertensive treatment on endothelium-dependent relaxations were studied in Dahl salt-sensitive (DS) and Dahl salt-resistant rats (DR) on a high or low sodium diet. The rats were given either a diet containing 8% NaCl or 0.1% NaCl for 8 weeks or a diet containing 8% NaCl and a combination of reserpine, hydrochlorothiazide, and hydralazine for 8 or 2 weeks. DS on the 8% NaCl diet developed hypertension, while the other rats did not. Antihypertensive therapy for 8 or 2 weeks prevented or reversed hypertension in DS and lowered blood pressure in DR on the 8% NaCl diet. Aortic rings with and without endothelium were suspended in organ chambers for isometric tension recording. In all groups, acetylcholine, adenosine 5'-diphosphate, and thrombin caused endothelium-dependent relaxations. The relaxations in response to all agonists were significantly decreased in DS on 8% NaCl compared to relaxations in the other rats. Antihypertensive treatment for 8 or 2 weeks prevented or reversed the decreased endothelium-dependent relaxations in response to all agonists tested, but not those to the endothelium-independent agonist, sodium nitroprusside. These results suggest that antihypertensive treatment normalizes endothelium-dependent relaxations. This effect of antihypertensive treatment might be important for the prevention of cardiovascular complications in patients with hypertension.

Biological variability in Wistar-Kyoto rats. Implications for research with the spontaneously hypertensive rat.

Abstract: The spontaneously hypertensive rat (SHR) initially bred in Kyoto is the most widely studied animal model of essential hypertension. As controls for the SHR, most workers have used normotensive descendants of Wistar rats from the colony in Kyoto from which the SHR strain was derived (Wistar-Kyoto rats, WKY). But the presumption that WKY are serviceable controls for SHR rests on the tacit assumption that all WKY constitute a single inbred strain. It appears, however, that whereas the National Institutes of Health distributed breeding stocks of SHR after they had been fully inbred (i.e., after 20 generations of brother-sister mating), the breeding stocks of WKY were distributed before they had been fully inbred. Accordingly, the biological variability of WKY may be greater than that of SHR. To investigate this possibility, we obtained SHR and WKY from two of the largest commercial suppliers in the United States and systematically measured the growth rate and blood pressure of these rats under identical physical and metabolic conditions. We found that WKY from one source differed from those of the other in both growth rate and blood pressure. In contrast, the SHR from the two suppliers were not different with respect to either growth rate or blood pressure. Because the National Institutes of Health may have distributed breeding stocks of WKY as early as the F6 generation, it is possible that rats currently designated as WKY do not constitute a single inbred strain. Thus, interpretation of studies employing "the Wistar-Kyoto rat strain" as a control for the SHR may be much more problematic than has previously been recognized.

Area postrema is critical for angiotensin-induced hypertension in rats.

Abstract: The effect of surgical ablation of the area postrema on acute (5-10 minutes) and chronic (5-10 days) increases in mean arterial pressure produced by intravenous infusion of angiotensin II in conscious, instrumented rats was studied. In agreement with previous studies, pressor responses of area postrema-ablated rats (n = 11) to acute angiotensin II infusion were identical to those of control sham-lesioned rats (n = 13). In these same rats, however, a 5-day infusion of angiotensin II produced a sustained hypertension in the sham-lesioned group whereas mean arterial pressure was increased only transiently (1-3 days) in the area postrema-ablated rats. No differences before infusion of arterial pressure, heart rate, water intake, urinary sodium excretion, and urinary potassium excretion were observed between sham-lesioned and area postrema-ablated rats; only arterial pressure was changed significantly during angiotensin II infusion in either group. Twenty-four hours after terminating angiotensin II infusion, mean arterial pressure was within the normotensive range in both sham-lesioned and area postrema-ablated rats. In a separate group of sham-lesioned (n = 13) and area postrema-ablated (n = 12) rats, angiotensin II was infused intravenously for a 10-day period; mean arterial pressure was increased significantly over the entire 10-day infusion in sham-lesioned rats, but for only 1 day in area postrema-ablated rats. An intact area postrema appears necessary for the development of chronic, but not acute, hypertension during intravenous infusion of angiotensin II in the rat.

Insulin and blood pressure during weight loss in obese adolescents.

Abstract: The role of insulin in the regulation of blood pressure was evaluated in 50 obese adolescents before and after a 20-week weight loss program. When compared with 10 nonobese adolescents, the obese subjects had significantly higher systolic, diastolic, and mean arterial pressures (p = 0.005), an elevated 24-hour urinary sodium excretion (p = 0.002), an elevated fasting insulin concentration (p = 0.001), and an abnormal insulin response to an oral glucose tolerance test (sum of the insulins at 0, 1, and 2 hours post-oral glucose load; p = 0.001). We also observed a significant correlation between systolic and diastolic blood pressure (age and sex normalized) and body weight (r = 0.57, p less than 0.01 and r = 0.7, p less than 0.01), fasting insulin (r = 0.49, p less than 0.01 and r = 0.54, p less than 0.01), and sum of insulins (r = 0.42, p less than 0.01 and r = 0.46, p less than 0.01). To study the effect of weight loss on the relationship between blood pressure and insulin, the obese subjects were randomly assigned to three groups: 15 to a diet and behavior change group, 18 to a diet, behavior change, and exercise group, and 17 to an obese control group. Compared with the obese control group, the two weight loss groups each experienced a significant decrease in insulin (p less than 0.01), sum of the insulins (p less than 0.01), and blood pressure (p less than 0.01). The decrease in blood pressure during the weight loss program significantly correlated with the change in both insulin and body weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence that prostacyclin mediates the vascular action of magnesium in humans.

Abstract: Evidence in vitro and in humans suggest that Mg2+ can alter systemic and renal vascular tone. However, the mechanism of these effects is not known. The role of vasodilator prostaglandin release and Ca2+ flux in Mg2+-induced changes in blood pressure and renal blood flow was studied in 10 normal subjects maintained on a fixed 80-mEq Na+ and K+ diet. Magnesium sulfate infused at 200 mg/hr for 3 hours reduced systolic and diastolic blood pressure within 1 hour (from 119 +/- 2 [SEM] to 109 +/- 4 mm Hg systolic; from 74 +/- 3 to 64 +/- 4 mm Hg diastolic; p less than 0.02). This hypotensive response was seen in all subjects and persisted for 3 hours. The pulse rate did not change, but renal blood flow (p-aminohippurate clearance) increased (from 902 +/- 78 to 1108 +/- 130 ml/min/1.73 m2; p less than 0.05). The Mg2+ infusion produced a significant increase in the excretion of the stable prostaglandin I2 (PGI2) metabolite 6-keto-PGF1 alpha (from 96 +/- 12 to 154 +/- 16 ng/g creatinine; p less than 0.01). In contrast, urinary PGE2 was not altered (328 +/- 75 vs 399 +/- 145 ng/g creatinine; p greater than 0.6). To evaluate the functional role of PGI2 release, the cyclooxygenase inhibitors indomethacin (75 mg) or ibuprofen (600 mg) were given before the Mg2+ infusion. Both cyclooxygenase blockers, given in doses that inhibited immunoreactive 6-keto-PGF1 alpha release, completely prevented the Mg2+-induced decline in blood pressure and increased renal blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Ventricular atriopeptin. Unmasking of messenger RNA and peptide synthesis by hypertrophy or dexamethasone.

Abstract: Left ventricular hypertrophy or treatment with dexamethasone caused a 2.5-fold to threefold increase in both immunoreactive atriopeptin (AP) and AP messenger RNA (mRNA), primarily in left ventricular tissue. The combined treatments increased immunoreactive AP and AP mRNA more than either treatment alone. In the animals in which cardiac hypertrophy had been produced by abdominal aortic constriction, there was a decrease in atrial levels of AP and an increase in plasma levels of immunoreactive AP. The increase in left ventricular immunoreactive AP was confirmed by immunohistochemical staining of tissue from hypertrophied and/or dexamethasone-treated rats. The mRNA accumulated in the left ventricle was identical to atrial AP mRNA, as judged by transcriptional start site and by size on Northern blots. Because the mass of ventricular tissue is substantially greater than that of atrial tissue, the induced mRNA levels may represent a total abundance approaching one third of the total AP mRNA in the atria. High performance liquid chromatographic purification of ventricular extracts primarily demonstrated the presence of the high molecular precursor and small amounts of C-terminal peptide AP. Induction of ventricular AP (mRNA and peptide) may represent regression of the tissue to an earlier developmental form. These data provide a unique example of regulation of AP biosynthesis in nonatrial tissue.

Structural and functional consequence of neonatal sympathectomy on the blood vessels of spontaneously hypertensive rats.

Abstract: Neonatal sympathectomy of spontaneously hypertensive rats (SHR) and control Wistar-Kyoto rats (WKY) was performed by a combined treatment with antiserum to nerve growth factor and guanethidine during the first 4 weeks after birth. The development of hypertension was completely prevented in the treated SHR: at 28 to 30 weeks of age, systolic blood pressure of treated SHR was 139 +/- 2 mm Hg as compared with 195 +/- 8 mm Hg in untreated SHR. The extent of sympathectomy was verified by histofluorescence. Fluorescence histochemistry for catecholamine-containing nerves showed a complete absence of adrenergic nerves in the mesenteric arteries of treated rats. A supersensitivity to norepinephrine was exhibited by mesenteric arteries, anococcygeus muscle, and tail arteries from the treated SHR and WKY. In the mesenteric vascular bed, maximal response to norepinephrine was significantly reduced by sympathectomy. Sympathectomy also abolished the responses (e.g., generation of excitatory junctional potentials) of tail arteries to electrical stimulation of perivascular nerves. Morphometric measurements of three categories of mesenteric arteries showed that sympathectomy had no effect on the hypertrophic change of smooth muscle cells in the conducting vessels, but it prevented the hyperplastic changes of the muscle cells from reactive, muscular arteries and small resistance vessels. These results suggest that one of the primary roles of the overactive sympathetic nervous system in the development of hypertension in SHR is manifested through its trophic effect on the arteries of SHR. This trophic effect appears to cause a hyperplastic change in the smooth muscle cells in the reactive and resistance vessels, thereby contributing to the development of hypertension in older SHR.

Left ventricular hypertrophy in hypertension. Prevalence and relationship to pathophysiologic variables.

Abstract: In less than a decade since development of echocardiographic measurement of left ventricular muscle mass, studies using this technique have provided considerable information about the prevalence and pathophysiology of left ventricular hypertrophy in human hypertension. Increased left ventricular mass has been found in a significant minority of patients with systemic hypertension, with the exact prevalence dependent both on how a population is selected and on the sex, race, and possibly age composition of its members. All published studies have reported that left ventricular hypertrophy is more closely related to blood pressure recorded in the patient's natural setting during normal activity or exercise-whether measured by portable recorder or home manometer-than to blood pressure measured by the physician. In addition, studies indicate that the classic hypertensive abnormalities of concentric left ventricular hypertrophy and increased peripheral resistance are interrelated, while left ventricular hypertrophy is absent in a subgroup of patients with mild essential hypertension who exhibit high cardiac output and evidence of supernormal myocardial contractility. Conversely, the left ventricular functional response to exercise is inversely related to the degree of hypertrophy. High levels of blood viscosity, which would tend to blunt the reduction in peripheral resistance expected during sleep or exercise, have also been associated with left ventricular hypertrophy in patients with essential hypertension. Echocardiographic studies have provided evidence both for and against the hypothesis that activity of the sympathetic or reninangiotensin systems plays a direct role in causing hypertensive cardiac hypertrophy. These findings demonstrate the useful role that echocardiographic assessment of left ventricular structure and function may play in hypertension research.

Electron spin resonance studies of erythrocytes from spontaneously hypertensive rats and humans with essential hypertension.

Abstract: The purpose of the present study was to investigate erythrocyte membrane abnormalities in hypertension by means of an electron spin resonance and spin-label technique. The erythrocytes from spontaneously hypertensive rats (SHR) and humans with untreated essential hypertension were examined and compared with their normotensive counterparts, and electron spin resonance spectra were obtained for a fatty spin-label agent (5-nitroxy stearate) incorporated into the erythrocyte membranes. The value of outer hyperfine splitting (2T' parallel) was significantly higher in erythrocytes of SHR and humans with essential hypertension than in erythrocytes of normotensive controls (at 37 degrees C: SHR, 56.14 +/- 0.51 gauss [G], n = 8; Wistar-Kyoto rats, 52.22 +/- 0.86 G, n = 4, p less than 0.01; humans with essential hypertension, 56.94 +/- 0.27 G, n = 11; normotensive subjects, 55.44 +/- 0.36 G, n = 8, p less than 0.01). The order parameter (S) was also increased in the hypertensive rats and humans compared to their respective normotensive controls. When calcium was loaded to erythrocytes with calcium ionophore A23187 (0.9 microM) and CaCl2 (1.0 mM), the parameters of the spectra were increased. These changes were more prominent in the hypertensive groups than in the normotensive controls. These results revealed that the erythrocyte membranes of the hypertensive subjects tolerated different spin motions than those of the normotensive controls in the electron spin resonance study and that membrane fluidity might be decreased in hypertension. Additionally, calcium loading to erythrocytes caused the reduction of membrane fluidity. Therefore, it is suggested that an abnormality of calcium handling at the cellular level might affect physical properties of the biomembranes in hypertension.

Arterial and venous compliance in sustained essential hypertension.

Abstract: Arterial and venous compliances are decreased in men with sustained essential hypertension. The reduced arterial compliance acts to maintain systolic pressure and end-systolic stress, thus contributing to the development of cardiac hypertrophy. Since cardiac output remains within the normal range in the hypertrophied hypertensive heart, elevated left ventricular pressures, and therefore increased cardiac filling pressures, are necessary if an adequate stroke volume is to be maintained. In hypertensive persons, reduced venous compliance acts to maintain the filling pressure of the heart in the presence of reduced intravascular volume. In patients with hypertension, even if compliance changes have been initiated by the elevated blood pressure itself, the reduced arterial and venous compliance observed in cross-sectional studies is not simply the mechanical consequence of the elevated blood pressure, but also reflects intrinsic alterations of the vascular wall. Consequently, blood pressure reduction caused by antihypertensive agents is not constantly associated with a reversion of the decreased vascular compliance. Such observations may be of importance in the consideration of cardiovascular morbidity and mortality in patients treated for hypertension.

Recommendations concerning use of echocardiography in hypertension and general population research.

Abstract: Use of echocardiography to quantify left ventricular structure and function requires standardization of recording conditions and techniques, accurate machine calibration, and definition of requirements for measurable images. Measurement of left ventricular muscle mass should use M-mode, two-dimensional, or three-dimensional echocardiographic methods that have been anatomically validated to maximize accuracy and comparability of results among studies. Body size and sex influence ventricular muscle mass sufficiently to be taken into account for clinical and research purposes, while age and physical activity are of less certain importance. Echocardiographic studies have clarified the prevalence of left ventricular hypertrophy in hypertensive patients and the effect of blood pressure during normal activity on left ventricular muscle mass, and they have provided data suggesting that left ventricular hypertrophy is a major cardiac risk factor in hypertensive and general populations. Further research is needed to obtain definitive results in these areas, to track the hitherto elusive transition from functionally compensated cardiac hypertrophy to congestive heart failure, and to determine the degree and selectivity of beneficial cardiac effects of antihypertensive treatment. Three-dimensional echocardiographic reconstruction and Doppler measurement of intracardiac blood flow and systemic hemodynamics are likely to extend the usefulness of echocardiography for hypertension and general population research.

Sex difference in the development of deoxycorticosterone-salt hypertension in the rat.

Abstract: To investigate a possible sex difference in the development of deoxycorticosterone (DOC)-salt hypertension in rats, systolic blood pressure was measured over 6 weeks in unilaterally nephrectomized male and female rats with or without DOC-salt treatment. Throughout the treatment, systolic blood pressure was significantly lower in female than in male DOC-salt rats (at the end of the sixth week: 190 +/- 8 vs 163 +/- 7 mm Hg, p less than 0.05). The difference in blood pressure was also confirmed by the direct measurement of mean arterial pressure at the end of the experiment. The 24-hour urinary excretion of vasopressin was significantly higher in male control rats than in female control rats; however, no difference was observed between male and female DOC-salt rats, in which the urinary excretion of vasopressin was four to five times higher than in control rats. The plasma vasopressin concentration was higher in DOC-salt rats, but there were no differences between sexes. There were no differences in the metabolic clearance rate of vasopressin among the four groups of rats. This indicates that the elevated plasma vasopressin concentration in DOC-salt hypertensive rats is due to increased release of the hormone, rather than to impaired metabolism. Thus, although vasopressin plays a pivotal role in the pathogenesis of DOC-salt hypertension, the sexual dimorphism in this form of hypertension cannot be attributed to differences in the secretion, metabolism, or plasma concentration of vasopressin.

Effects of race and marginally elevated blood pressure on responses to stress

Abstract: A total of 228 men, aged 18 to 22 years (109 black and 119 white), underwent monitoring of heart rate (HR) and systolic (SBP) and diastolic blood pressure (DBP) responses during several stressor conditions and a 30-minute posttask rest period Stressors included the cold pressor test and three reaction-time tasks: noncompetitive, competitive, and competitive plus money incentive Substantial within-subject variations in blood pressure and heart rate were induced, varying from 119/70 to 148/94 mm Hg and from 63 to 91 beats/min on the average Men (25 black and 39 white) with marginal SBP elevations during initial casual determinations had higher SBP under all conditions compared with men whose casual SBP levels were normal, and they also showed greater elevations over baseline levels in heart rate, SBP, and DBP during the stressors and the initial casual determination Black and white subjects did not differ in their blood pressures at baseline or during the initial casual determinations, although blacks had slightly lower heart rates Blacks did show greater SBP elevations over baseline levels than whites during the stressors, primarily because the blacks with marginally elevated SBP showed substantially greater stress-induced increases than whites with marginally elevated SBP This enhanced pressor response to stress in blacks with marginal blood pressure elevations may be due to higher vascular resistance during enhanced sympathetic activity and could contribute to the higher incidence of hypertension among blacks

Body fat patterning and blood pressure in children and young adults. The Bogalusa Heart Study.

Abstract: The relationship of central body fat (measured by subscapular skinfold) and peripheral body fat (measured by triceps skinfold) to blood pressure was investigated in 3784 subjects aged 5 to 24 years old from the biracial community of Bogalusa, Louisiana. After adjustment for height, age, sex, and race, significant relationships were found for both central body fat (r = 0.19 and 0.14, p less than 0.0001) and peripheral body fat (r = 0.15 and 0.12; p less than 0.0001) with systolic and diastolic (fourth phase) blood pressure, respectively. However, the relationship between peripheral body fat and blood pressure, after controlling for the level of central body fat, was negligible (r = 0.00 and 0.01 for systolic and diastolic blood pressure, respectively). In contrast, the central body fat-blood pressure relationship remained statistically significant even after controlling for the peripheral body fat level. For central body fat, the partial correlations with systolic blood pressure were highest in young children (r = 0.15), dropped slightly during adolescence (r = 0.12), and became nonsignificant only in 18- to 24-year-old female subjects; correlations remained high in both black and white 18- to 24-year-old male subjects (r = 0.18 and 0.16, respectively). Mean levels of systolic blood pressure from the lowest to the highest quartile of central body fat ranged from 100.4 to 108.9 mm Hg. The adult hypertension-central body fat relationship, which has been shown by others, appears to exist in children. Continued efforts at early identification and prevention of obesity in children are warranted.

Reproducibility of echocardiographic left ventricular measurements.

Abstract: Serial echocardiograms with acceptable reproducibility of measurements may be produced by careful performance and interpretation of the studies. The following recommendations have been shown to enhance reproducibility. Strict adherence to quality control is necessary to generate echocardiograms of the highest technical quality. Sonographers should be aware of the definition of a technically adequate study--including correct beam or plane angulation and continuous visualization of interfaces--and seek this ideal in every study. Participation by the sonographer in performance of measurements enhances recognition of the requirements for accurate quantitative echocardiography. Regular machine calibration is a prerequisite to accurate quantitative echocardiography. Considerable effort must be made to standardize the position of each acoustic window and angulation from which the patient is imaged--with deviation from these norms being recorded for future reference. If at all possible, measurements should be taken at end expiration. If that is not possible, measurement of several consecutive beats will limit the impact of respiratory variation. A uniform convention of measurement should be adopted. The best candidates for M-mode measurements are the American Society of Echocardiography recommendations for general measurement and the Penn convention for calculation of M-mode left ventricular mass. Further data is needed to determine which approaches to two-dimensional measurements best combine accuracy and reproducibility. Interpretation of echocardiograms may be made most reproducible by measuring pertinent parameters from multiple beats and using the mean as the result and by having at least two readers interpret each echocardiogram, possibly with two separate readings by each reader.

Plasma angiotensins and blood pressure during converting enzyme inhibition.

Abstract: The relationship between plasma angiotensin and the reduction of blood pressure with the angiotensin converting enzyme inhibitor enalapril was studied in rats. Blood pressure was measured in conscious rats with indwelling arterial catheters. To measure angiotensin II, plasma was analyzed by physical separation of angiotensins using high performance liquid chromatography followed by radioimmunoassay. The effects of both single (acute) and long-term (chronic) dosages of enalapril were measured. After a single oral dose of enalapril (10 mg/kg), mean arterial pressure fell from 111 +/- 3 to 86 +/- 3 mm Hg (p less than 0.005). Despite the blood pressure reduction, plasma angiotensin II was unaffected (control, 9.9 +/- 1.8 vs 9.7 +/- 1.1 pg/ml). After a higher single oral dose of enalapril (30 mg/kg), there was a reduction in both mean arterial pressure (81 +/- 5 mm Hg, p less than 0.005) and plasma angiotensin II concentration (2.3 +/- 0.6 pg/ml, p less than 0.01). The chronic effects of converting enzyme inhibition were evaluated in rats given enalapril in their drinking water (30 mg/kg 24 hr) for 1 week or 2 months. Mean arterial pressure remained equally low after chronic administration (for 1 week or 2 months), but plasma angiotensin II increased above normal (after 1 week, 28.9 +/- 8.7, p less than 0.01 vs control; after 2 months, 43.1 +/- 16.2 pg/ml, p less than 0.05 vs control). Although plasma angiotensin converting enzyme activity was undetectable at any time after enalapril administration, there was a partial return of the angiotensin I pressor response with chronic administration. The data are most compatible with actions of converting enzyme inhibitors independent of the blockade of plasma angiotensin II formation.

Intracellular calcium and sodium in hypertensive patients.

Abstract: Untreated subjects with mild to moderate hypertension were compared with normotensive controls recruited from the same ambulatory screening clinic. All subjects were black. Resting levels of cytosolic free calcium were estimated in washed platelets with the fluorescent intracellular probe fura 2, and sodium and potassium were measured in red blood cells. Calcium levels were 21% higher in the hypertensive subjects (p = 0.02), and a 9% increase in sodium was observed in an expanded sample (p = 0.04). Neither intracellular calcium nor intracellular sodium had a significant linear correlation with blood pressure when hypertensive subjects and controls were examined separately or when the two groups were combined. Potassium was slightly but not significantly increased in hypertensive subjects. Among the participants for whom both calcium and sodium measurements were available, a weak, nonsignificant correlation between these ions was noted (r = 0.2; n = 48). This correlation was significant among participants in the control group examined separately (r = 0.3; n = 33; p = 0.05). Although the measurements were performed in different cell lines, these findings demonstrate increases in both intracellular calcium and sodium in hypertensive humans.

Multiple Effects of Calcium Entry Blockers on Renal Function in Hypertension

Abstract: Characterization of the renal effects of calcium entry blockers has not been easy because the inhibition of Ca2+ cellular influx alters several regulatory functions. The ability of calcium blockers to dilate renal vasculature and to increase glomerular filtration rate is largely determined by the preexisting vascular tone. However, the increments in sodium excretion could occur without alterations in renal hemodynamics. Calcium blockers could increase sodium excretion by inducing a redistribution of renal blood flow toward juxtamedullary nephrons, by inhibiting tubuloglomerular feedback responses, or by a direct action on the tubular transport of sodium. These effects are poorly understood at present. In vitro studies show that the blockade of calcium entry enhances renin secretion and decreases prostaglandin synthesis. This dissociation has not been found during long-term administration, which has been proved to be effective for the treatment of essential hypertension with normal maintenance of renal function. In this respect, there are reports indicating that calcium blockers are particularly effective in a subgroup of patients with essential hypertension who exhibit subtle but detectable alterations in calcium metabolism. Further studies are needed to determine whether this significant response to calcium blockers is due to correction of an early defect of calcium cellular kinetics that initiated the increase in blood pressure.

Glucocorticoids modulate vascular reactivity in the rat.

Abstract: To clarify the role of endogenous glucocorticoids in the regulation of blood pressure, the cardiovascular effects of RU 486, a steroid derivative with antiglucocorticoid properties, were investigated in Wistar rats. Pressor responses to angiotensin II (Ang II), norepinephrine, and vasopressin were studied in normal conscious rats before and after administration of RU 486. At 20 mg/kg/day, RU 486 significantly blunted pressor responses to Ang II and norepinephrine, whereas those to vasopressin were not greatly affected. At a lower dose, RU 486 did not alter pressor responses; at a higher dose, it augmented them, probably through its agonistic glucocorticoid effect. At 20 mg/kg/day, RU 486 antagonized the enhancing effect of a glucocorticoid agonist on pressor responses to Ang II, norepinephrine, and vasopressin. Cardiac output and renal blood flow were measured in anesthetized rats by the microsphere method. RU 486 at 20 mg/kg/day did not alter basal cardiac output and renal blood flow. RU 486 pretreatment attenuated pressor responses to Ang II and norepinephrine but did not alter cardiac output. It significantly blunted the decrease in renal blood flow and the increase in renal vascular resistance induced by Ang II. In rats fed a low sodium diet (where the pressor systems are stimulated), administration of RU 486 (20 mg/kg/day for 5 days) decreased total peripheral vascular resistance by 29% and mean blood pressure by 20 mm Hg. This effect was unrelated to any antimineralocorticoid activity of the compound, as shown by unchanged urinary sodium excretion, sodium balance, and plasma renin concentration. In contrast, it was due to the antiglucocorticoid activity, as shown by restoration of mean blood pressure by corticosterone, the major glucocorticoid in rats. Renal vascular resistance decreased during RU 486 administration in anesthetized (-25%) and unanesthetized (-19%) rats. Glomerular filtration rate, estimated from inulin clearance in conscious rats, did not change significantly. In conclusion, the present results suggest that endogenous glucocorticoids increase vascular reactivity and therefore contribute to blood pressure regulation. They also participate in the control of renal hemodynamics. This effect is most apparent in salt-restricted rats. The vascular action of glucocorticoids was unmasked by the administration of the antiglucocorticoid compound RU 486.