Showing papers in "Clinical and Experimental Hypertension in 1996"

The Evidence for a Pathophysiologic Significance of the Sympathetic Overactivity in Hypertension

Abstract: Interest for the role of the sympathetics in the genesis of hypertension has come full circle from early enthusiasm, through a period of neglect, to present understanding that strong evidence cannot be ignored. Sympathetic overactivity starts in childhood and is easily evident in 30% of patients with incipient hypertension. Later, in advanced hypertension, altered cardiovascular responsiveness obscures the obvious signs of sympathetic overactivity but the brain maintains its decisive pathophysiologic role. The early onset, the bimodal distribution of the neurogenic "hyperkinetic" pattern and familial aggregation suggest a genetic component in sympathetic overactivity. Patients with hypertension are at high risk for coronary disease and some of that risk is not directly related to blood pressure elevation. High sympathetic tone explains the pathophysiology of "pressure-independent" risk for premature coronary atherosclerosis in hypertension and for excess mortality/morbidity in patients who had already developed coronary heart disease.

Compliance with Antihypertensive Treatment

Abstract: Compliance to antihypertensive treatment is a critical factor conditioning the success of therapy. It has been calculated that, depending on the method used to monitor compliance, only 20 to 80% of treated hypertensives can be considered as good compliers.In the past years it was thought that compliance was only a patient's problem but instead, the role of the physician in determining patient's compliance is very important. He should give clear information about the risks of the disease, the advantages of therapy and how to take medicines. He should also prescribe a therapeutic scheme as simple as possible avoiding multiple drug administrations and informing patients about possible side-effects. Subjects at particular risk of poor compliance (middle aged males, still active in work, without previous cardiovascular diseases) must be particularly monitored. In any case of poor response to therapy it is important to suspect poor compliance.A standardization of the methods for recording compliance is needed e...

Adrenomedullin: changes in circulating and cardiac tissue concentration in Dahl salt-sensitive rats on a high-salt diet.

Abstract: Adrenomedullin (AM), a novel hypotensive peptide, is suggested to be involved in defense mechanisms against hypertension, however, the detail mechanisms have not been clarified. To elucidate whether AM synthesis would be altered in a salt dependent hypertension, we have investigated the AM concentration and AM messenger RNA (mRNA) level in tissues of Dahl salt-sensitive rats on either low- or high-salt intake. The AM concentration in cardiac ventricle of the high-salt group was significantly higher than that of the low-salt group. The plasma AM concentration was also significantly higher in the high-salt group than in the low-salt group. Furthermore, the plasma AM concentration correlated well with the weight of left ventricle. RNA blot analysis revealed that the AM mRNA level in cardiac ventricle of the high-salt group was higher than that of the low-salt group. These results suggest that AM participates in the pathophysiology of salt dependent hypertension and plays a role in cardiac hypertrophy.

High potassium diets reduce vascular and plasma lipid peroxides in stroke-prone spontaneously hypertensive rats.

Abstract: We examined the effect of high potassium (K) diet on oxidative stress to endothelium in hypertensive rats. Five-week-old stroke-prone spontaneously hypertensive rats (SHRsp) were fed a 5% high NaCl diet containing either 0.5% normal K (n = 28) or 2.1% high K (n = 19) for 6 weeks, and lipid peroxides in the aortic intima and plasma were measured. Lipid peroxides were extracted into an organic solvent to avoid the interference of carbohydrates or glycoproteins, and malondialdehyde (MDA) produced from lipid peroxides by acid-heating was measured by its reaction to thiobarbituric acid. The antioxidant butylated hydroxytoluene prevented spurious lipid peroxide formation during the whole procedure, and optimum Fe3+ allowed a maximum MDA production from lipid peroxides. The high K SHRsp showed lower lipid peroxide levels than the normal K SHRsp both in the intima (5.6 +/- 0.3 vs. 7.2 +/- 0.4 nmol MDA/mg fatty acids, p < 0.003) and plasma (0.91 +/- 0.08 vs. 1.46 +/- 0.10 nmol MDA/ml, p < 0.001). Mean arterial pressure was slightly lower by 13 mmHg in the high K SHRsp, but these differences were still obvious even when we compared groups of rats with precisely matching blood pressures. These results indicate that high K diets reduce oxidative stress on the endothelium of high NaCl-fed SHRsp independently of blood pressure changes. This effect may be involved in the mechanism by which high K diets protect endothelium and reduce stroke incidence in hypertensive animals. Thus, we improved the method of lipid peroxide measurement and propose the protective effects of high K diet against oxidative stress to endothelium in hypertension animals.

Vascular Reactivity to Phenylephrine and Angiotensin II in Hypertensive Rats Associated with Insulin Resistance

Abstract: Previous reports suggest that when rats are fed a carbohydrate-enriched diet they develop hyperinsulinemia associated with elevated blood pressure. The purpose of this study was to assess the vascular reactivity of fructose-treated rats to various pressor agents. Male Sprague Dawley rats (n=24) were used for this study and were divided into two equal groups. One of the groups was fed normal rat chow and served as the control group, whereas the other group was fed a fructose-enriched diet for four weeks. Mean blood pressure was elevated in the fructose-treated rats at the end of the second week of fructose treatment and remained elevated for the remainder of the study. At the end of the second and fourth weeks of fructose treatment, six rats from each group were used to assess both in vivo and subsequently in vitro vascular reactivity to various pressor agents. The jugular vein and carotid artery were cannulated under anesthesia. Twenty four hours after recovery from surgery pressor responses to angiotensi...

Relation of 24-Hour Ambulatory Blood Pressure and Short-Term Blood Pressure Variability to Seasonal Changes in Environmental Temperature in Stage I Hypertensive Subjects. Results of the Harvest Trial

Abstract: We investigated the seasonal changes in blood pressure (BP) and in short-term BP variability determined using ambulatory blood pressure monitoring (ABPM) 1000 white subjects, who took part in the multicenter HARVEST study, underwent ABPM with the A&D TM-2420 or the Spacelabs 90207 Standard deviation of the mean daytime and nighttime BP was taken as an index of short-term BP variability (v) Maximal outdoor temperature (Tmax) during each ABPM was obtained from local Meteorological Centers Subjects were divided according to season and to quartiles of Tmax A subgroup of 46 persons who repeated ABPM in Winter and Summer was also studied We observed evident seasonal differences in office and ambulatory systolic BP (SBP) with a peak during Winter Diastolic BP (DBP) and heart rate did not vary throughout the four seasons Office SBP (p < 001), 24-hour (p < 0002), daytime SBP (p < 00001), both daytime SBPv (p < 00001), DBPv (p < 002), and nighttime SBPv (p < 005), DBPv (p < 002) as well as norepinephrine (p < 0005) were significantly higher during Winter than Summer Similar differences were observed in subjects grouped in quartiles of Tmax In the subgroup daytime but not nighttime SBP was higher in the cold season Average 24-hour SBP (p < 005), daytime SBP (p < 002), daytime SBPv (p < 0001) and DBPv (p < 005) and norepinephrine (p < 00001) were significantly negatively correlated with Tmax in the whole population BP is higher and subjected to wider oscillations during the cold season in patients with mild hypertension probably due to sympathetic activation The assessment of a hypertensive subject may give different results according to the season

Selective Neural Regulation of Epinephrine and Norepinephrine Cells in the Adrenal Medulla-Cardiovascular Implications

Abstract: The innervation of the adrenal medulla regulates the release of catecholamines from the two, epinephrine (EPI) and norepinephrine (NE), populations of chromaffin cells. Adjustments in the neural output to the adrenal medulla are made by centers in the brain that integrate the sensory input arising from a variety of challenges and the resulting changes in secretion assist in the restoration of homeostasis. Interestingly, the adrenal medullary secretory responses do not simply reflect increments a fixed ratio of EPI to NE as might be expected if release was proportional to the number EPI and NE cells. Instead, the ratio of EPI to NE changes depending on the magnitude and type of stimulus that initiates neural activation of the medulla. The variability in the EPI:NE release ratio implies that the EPI and NE cells can be differentially stimulated. Although the underlying mechanisms are not fully characterized, this review presents an emerging view that the selective control of EPI and NE cells is accounted for, first, by the existence of separate neural circuits between brain centers and the chromaffin cells, and second, through neuromodulation that selectively influences EPI and NE cells. The presence of mechanisms that allow for separate control of the EPI and NE cells may significantly augment the range of cardiovascular and metabolic responses mediated through activation of the adrenal medulla.

AT1 receptor density changes during development of hypertension in hyperinsulinemic rats.

Abstract: In a previous study we showed that the renin-angiotensin system (RAS) plays a role in the etiology of fructose-induced hypertension. To our knowledge, no previous study has evaluated changes in angiotensin II (Ang II) type I receptor (AT1) density in fructose-fed rats that are insulin resistant and hypertensive. The purpose of this study was to determine the changes in plasma Ang II and AT1 density associated with the elevation of blood pressure in fructose-treated rats. Male Sprague-Dawley rats were divided into two groups and were fed either normal rat chow or a 60% fructose-enriched diet for four weeks. Plasma Ang II and serum insulin levels of the fructose-treated rats were significantly elevated (p<0.01) by the end of the second week of fructose treatment. Plasma Ang II levels of the fructose-fed rats returned to basal levels by the end of the fourth week of dietary treatment, whereas the serum insulin levels consistently remained elevated. Blood pressure was significantly elevated in the fructose-fe...

Evaluation of hemodynamics, vascular reactivity and baroreceptor compensation in the insulin resistant Zucker obese rats.

Abstract: Incidence of essential hypertension has been reported to be significantly higher in the population afflicted with non-insulin dependent diabetes mellitus (NIDDM). The present studies were under taken in the insulin resistant, Zucker obese rats to evaluate various factors that could lead to the development of high blood pressure. Direct blood pressure measurements in the conscious obese rats indicated that they were not consistently hypertensive although the blood pressures of the obese rats tended to be higher than that of the control lean rats. However, after Inactin anesthesia blood pressures of the obese rats were significantly elevated which can be related to an increase in sympathetic tone since autonomic ganglionic blockade eliminated the differences between the pressures of the two groups. Under anesthesia, cardiac output per 100 gm body weight was significantly lower indicating inadequate tissue perfusion in the obese rats. In a separate series of studies carried out in conscious rats, reflexly mediated alterations in the heart rate to intravenous phenylephrine and sodium nitroprusside were significantly blunted in the obese rats. These observations which include enhanced central sympathetic discharge, inadequate systemic hemodynamics and attenuation of baroreceptor compensation collectively suggest that the insulin resistant obese rats are in a pre-hypertensive state and could develop sustained hypertension if they are exposed to other risk factors.

Altered Arachidonic Acid Metabolism Contributes to the Failure of Dopamine to Inhibit Na+, K+-ATPase in Kidney of Spontaneously Hypertensive Rats

Abstract: Dopamine decreases tubular sodium reabsorption in part by inhibition of Na+, K+-ATPase activity in renal proximal tubules. The signaling mechanism involved in dopamine-mediated inhibition of Na+, K+-ATPase is known to be defective in spontaneously hypertensive animals. The present study was designed to evaluate the role of phospholipase A2 (PLA2) and its metabolic pathway in dopamine-induced inhibition of Na+, K+-ATPase in renal proximal tubules from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Renal proximal tubular suspensions were prepared and Na+, K+-ATPase activity was measured as ouabain-sensitive adenosine triphosphate hydrolysis. Dopamine inhibited Na+,K+-ATPase activity in a concentration (1 nM - 10 μM)-dependent manner in WKY rats while it failed to inhibit the enzyme activity in SHR. Dopamine (10μM)-induced inhibition of Na+,K+-ATPase activity in WKY rats was significantly blocked by mepacrine (10 μM), a PLA2 inhibitor, suggesting the involvement of PLA2 in dopamine-mediat...

Alterations in Mitochondrial DNA and Enzyme Activities in Hypertrophied Myocardium of Stroke-prone SHRS

Abstract: To clarify the pathophysiological alteration of mitochondria in SHRSP hypertrophied heart, mitochondria-related enzyme changes were examined and compared to those in WKY. Furthermore, the structure alteration in mitochondrial DNA (mtDNA) was examined by restriction fragment length polymorphisms (RFLPs). Both isocitrate dehydrogenase (ICDH) and cytochrome c oxidase (COX), which are related to energy production or the respiratory chain in mitochondria, were significantly lower in SHRSP myocardium than in WKY. Furthermore, superoxide dismutase (SOD), a potent radical scavenger, was also lower in SHRSP myocardium. RFLPs analysis by Rsa I revealed two deletions in the electrophoretic band in the SHRSP myocardium, but not in the liver. These findings suggest that mitochondrial dysfunction, especially lower energy production, could be an important factor for the pathogenesis of further myocardial degeneration. The results also suggest that mitochondrial alterations, in the membrane system as well as mtDNA, may be caused by oxidative stress in mitochondria because of decreased scavenging activity.

Primary and secondary prevention of stroke

Abstract: Data from prospective observational studies indicate that usual levels of blood pressure are directly and continuously related to the risk of stroke. a prolonged difference in usual diastolic blood pressure levels of just 5 mmHg would eventually confer about a one-third difference in stroke risk, with similar proportional effects in hypertensives and non-hypertensives. The results of randomised trials of blood pressure lowering drugs in hypertensive patients suggest that much or all of this long-term potential stroke avoidance can be achieved within just a few years of beginning treatment. Overall in 17 randomised trials of antihypertensive treatment, a net blood pressure reduction of 10-12 mmHg systolic and 5-6 mmHg diastolic, conferred a reduction in stroke incidence of 38% SD 4, with similar reductions in fatal and non-fatal stroke. Additionally, the sizes of the reductions were similar in trials in mild, moderate or more severe hypertension, in trials in older or younger patients and in trials in patients with or without a history of cerebrovascular disease. Because the proportional effects of treatment were similar in all these groups, the absolute effects of treatment on stroke varied in direct proportion to the background risk of stroke. The greatest benefits were, therefore, observed among those with a history of cerebrovascular disease, those above the age of 60 years, and those with more severe hypertension.

High Level of Circulating Human Tissue Kallikrein Induces Hypotension in a Transgenic Mouse Model

Abstract: We established a unique transgenic mouse model with liver-targeted expression of human tissue kallikrein using a mouse albumin enhancer and promoter. Northern blot analysis and ELISA showed that human tissue kallikrein was predominantly expressed in the liver of transgenic mice and secreted into the circulation at a high level. The transcript was also detected in the kidney, pancreas, salivary gland and heart at a low level by reverse transcription-polymerase chain reaction followed by Southern blot analysis. Systolic blood pressures were measured by the tail-cuff method, all three inde endent transgenic 83.1f0.8 mmHg, n = 13, P < 0.01) compared with the control mice (100. 9kO. 9 mmHg, n = 17). Administration of aprotinin, a potent tissue kallikrein inhibitor or Hoe 140, a bradykinin receptor antagonist, restored the blood pressure of transgenic mice but had no significant effect on control littermates. These studies show that over-production of tissue kallikrein in the circulation plays a role in blood p...

Uric acid, xanthine oxidase and other risk factors of hypertension in normotensive subjects.

Abstract: Uric acid produced by xanthine oxidase (also a source of superoxide radicals) has been known to increase in hypertensive patients. In this study we evaluated the possible involvement of uric acid and xanthine oxidase in the pathogenesis of hypertension by examining their association with mean arterial pressure (MAP) and factors related to blood pressure. These factors include age, quetelet index (weight/height2), cholesterol, creatinine, calcium (Ca), magnesium (Mg), sodium (Na), potassium (K) and urea. Fifty Two (male-19, female-33) normal healthy individuals were studied. Correlation studies of demographic variables showed that age was positively correlated with MAP [r = 0.309, p = 0.026] and cholesterol [r = 0.503, p = 0.000] while quetelet index was positively correlated with age [r = 422, p = 0.000] MAP [r = 0.331, p = 0.016] and xanthine oxidase [r = 0.331, p = 0.016]. MAP was positively correlated with uric acid [r = 0.511, p = 0.000], cholesterol [r = 0.492, p = 0.000] and xanthine oxidase enzyme activity [r = 0.388, p = 0.004] and negatively correlated with plasma calcium [r = 0.603, p = 0.000]. Correlation studies of measured parameters with uric acid and xanthine oxidase showed that uric acid was positively correlated with creatinine [r = 0.627, p = 0.000], plasma magnesium [r 0.442, p = 0.001] and negatively correlated with plasma calcium [r = 0.546, p = 0.000] while xanthine oxidase was negatively correlated with plasma calcium [r = -0.404, p = 0.003] and plasma sodium [r = -0.288, p = 0.038]. Stepwise multiple regression with MAP as dependent variable showed that 65% of total variability of blood pressure can be accounted for by plasma calcium, cholesterol, creatinine, plasma K, plasma Na, uric acid and xanthine oxidase in order of increasing R2 [xanthine oxidase: T-value = 3.26, R2 = 0.653]. It can be concluded that in normotensive subjects, uric acid and xanthine oxidase have significant association with blood pressure and thus are one of the many factors which are involved in the cause or effect of hypertension.

Insulin sensitivity in the pathogenesis of hypertension and hypertensive complications.

Abstract: Epidemiologic and clinical studies suggest an association between hyperinsulinemia (and insulin resistance) and hypertension. This relationship is not present in secondary forms of hypertension and may persist despite adequate antihypertensive therapy. Normotensive offspring of hypertensive parents are also, as a group, insulin resistant and hyperinsulinemic. The association of hyperinsulinemia (and insulin resistance) with hypertension is more marked in the obese but present in lean hypertensives as well. Physiological mechanisms by which insulin might increase blood pressure include sympathetic nervous system stimulation and enhancement of renal sodium reabsorption. Evidence exists linking both of these mechanisms to hypertension. Insulin is also independently associated with myocardial infarction and microalbuminuria, two long term complications of high blood pressure. Experimentally induced decreases in insulin resistance and hyperinsulinemia, furthermore, have been associated with decreased blood pre...

Pathogenetic Factors in Hypertension Endothelial Factors

Abstract: In normotensive humans, endothelium modulates vascular tone mainly by the production of nitric oxide. In human essential hypertension the basal release of nitric oxide is reduced and forearm vasodilation to the endothelium-dependent agonists acetylcholine or bradykinin is blunted. Defective basal release of nitric oxide seems to be secondary to blood pressure increase while impaired agonist-evoked endothelium-dependent vasodilation is probably a primary phenomenum. This latter endothelial dysfunction seems to be caused by the simultaneous presence of an alteration in the L-arginine-nitric oxide pathway and the production of constrictor prostanoids. Defective nitric oxide production is already detectable in normotensive offspring of hypertensive patients and young essential hypertensive. In contrast, vasoconstrictor prostanoid production seems to be associated with aging. In essential hypertensive patients, although only scanty data are available, chronic effective pharmacological treatment seems to restore impaired basal production of nitric oxide but does not improve vascular response to endothelial agonists.

Angiotensin I converting enzyme gene cosegregates with blood pressure and heart weight in F2 progeny derived from spontaneously hypertensive and normotensive Wistar-Kyoto rats.

Abstract: The present investigation examines the association of angiotesin I converting enzyme (ACE) genotypes with blood pressure and heart weight in an F2 population of rats derived from a cross between spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. ACE genotype of rats in the F2 population was determined using a microsatellite polymorphism. Our investigation revealed that cardiac mass was not correlated with blood pressure at 12 weeks of age within the SHR, WKY, F1 or F2 groups of rats. In male rats, ACE genotype accounted for approximately 20% of the difference in mean blood pressure between SHR and WKY rats. There was no effect in females. It was also responsible for 21%-29% of the difference in heart weight both in female and male animals. The allele derived from the SHR parent appeared recessive to the allele from WKY parent for both heart weight and blood pressure. These results suggest that a gene in the region of the ACE locus is one of the genetic factors influencing blood pressure an...

Hypertension, thermotolerance, and the "African gene": an hypothesis.

Abstract: Hypertension is a polygenic disease of world-wide concern. So far, no polygenic disease has been solved at the genetic level. Ethnic differences in the prevalence of hypertension may suggest candidate genes worthy of study. A strong genetic predisposition to hypertension and target organ damage appears to correlate with African ancestry, referred to as “the African gene.” Sub-Saharan Africans have endured the selective pressure of extreme heat for thousands of generations. Polymorphisms in the renin-angiotensin system, such as the recently described insertion/deletion polymorphism in the angiotensin I converting enzyme (ACE) gene, may predispose to hypertension and related disorders because of an advantage they confer in thermoregulation.

Evaluation of arterial compliance in humans

Abstract: Compliance is a measure of the elastic properties of arterial vessels and is a function of blood pressure. In recent years new techniques have been developed which allow to measure arterial compliance non invasively and continuously over the range of existing blood pressure values. It has been thus possible to investigate the alterations of arterial compliance in a variety of diseases and to address the physiological factors involved in arterial compliance modulation. This article will focus on the new data available on these issues.

Prevalence of hypertension and rate of blood pressure control as assessed by home blood pressure measurements in a rural japanese community, ohasama

Abstract: A cross-sectional community survey using home blood pressure measurements was performed in northern Japan to estimate the prevalence of definite hypertension, white coat hypertension and the success of blood pressure control in patients receiving antihypertensive drugs. A total of 1334 subjects (mean age +/- SD, 53.8 +/- 17.3 years; 8-91 years) participated in the screening and home blood pressure measurement program. They measured blood pressure at home at least 3 times (mean measurement frequency, 20.8 +/- 8.3 times). Of these 1334 subjects, 314 (65.1 +/- 8.9 years) were taking drugs (treated group) while 1020 (50.3 +/- 17.8 years) were not (untreated group). The WHO criteria were used to categorize screening blood pressure. Criteria for diagnosis of hypertension by home blood pressure measurements were as follows: definitely hypertensive (systolic blood pressure > or = 144 mmHg and/or diastolic blood pressure > or = 89 mmHg) and normotensive (104 < systolic blood pressure < or = 131 mmHg and 60 < diastolic blood pressure < or = 79 mmHg). Of the 1018 subjects identified as normotensive on screening measurements, home measurements indicated that 73 (7.2%) were hypertensive and 765 (74.7%) were normotensive or lower. Of the 112 subjects identified as hypertensive on screening measurements, home measurements showed that 42 (37.5%) were hypertensive and 30 (26.8%) were normotensive or lower. Of the 314 treated subjects, 45 (14.3%) were identified as hypertensive by screening measurements and 88 (28.0%) as hypertensive by home measurements. Only 20 (44.4%) of the former 45 subjects were also defined as definitely hypertensive by home measurements. Of the 1020 untreated subjects, 67 (6.6%) were hypertensive by screening measurements and 84 (8.2%) by home measurements. Only 22 (32.8%) of the former 67 subjects were classified as hypertensive by home measurements. Of the 67 untreated subjects identified as hypertensive by screening measurements, 20 (29.9%) were normotensive or lower by home measurements, suggesting that these subjects were "white coat" hypertensives. The study first confirmed based on the large community data that there are large discrepancies between screening (casual) blood pressure and home blood pressure measurements for recognition of hypertension and normotension. Determination of blood pressure levels by home blood pressure measurements may predict prognosis of hypertension differently from that by screening blood pressure measurements. Further prospectively study is needed to validate the prognostic value of home blood pressure measurements.

Antiatherosclerotic Effects of Antihypertensive Drugs: Recent Evidence and Ongoing Trials

Abstract: The issue as to whether antihypertensive drugs may exert some antiatherosclerotic effect, at least partly independent of blood pressure lowering, has been explored in several experimental models of atherosclerosis, and a large body of evidence has been obtained in favor of a specific antiatherosclerotic action of calcium antagonists and ACE-inhibitors. On the clinical side, several studies are investigating the problem in hypertensive patients in whom progression of carotid intima-media thickness (IMT) and atherosclerotic plaques is explored by sensitive quantitative B-mode ultrasound techniques. The MIDAS has indicated a slower progression, at least in the first six months, of carotid plaques in isradipine treated patients than in diuretic-treated ones. However, MIDAS as a pioneer study has been particularly valuable in giving information on the rate of growth of IMT in hypertensive patients and on the best end-point to use in carotid ultrasound trials. Baseline data of the ongoing studies ELSA and VHAS ...

Role of the circulating renin-angiotensin system in the pathogenesis of hypertension in transgenic rats. TGR(mREN2)27.

Abstract: Transgenic rats, termed TGR(mREN2)27, which carry the mouse ren2d renin gene, develop fulminant hypertension. To evaluate the role of the circulating renin-angiotensin system (RAS) in hypertension of TGR(mREN2)27, we determined plasma levels of its components and their regulation by ether-stress. Plasma prorenin was elevated in prehypertensive and in adult heterozygous TGR(mREN2)27 (fourtyfold), when compared with Sprague Dawley (SD) controls, whereas plasma renin concentration (PRC) and angiotensin II were not in SD rats ether anesthesia increased PRC at day (11 a.m.; fivefold), but not at night (11 p.m.). Ether had no effect on PRC in TGR(mREN2)27. In contrast, ether increased plasma corticosterone levels at day and night in both strains to a similar degree. Our data indicate that plasma active renin is not a pathogenetic factor for hypertension in TGR(mREN2)27 and suggest a primary role of circulating prorenin. The lack of stimulation of PRC by ether in TGR(mREN2)27 probably reflects predominant extrarenal origin of renin.

Effects of Early Captopril Treatment and Its Removal on Plasma Angiotensin Converting Enzyme (ACE) Activity and Arginine Vasopressin in Hypertensive Rats (SHR) and Normotensive Rats (WKY)

Abstract: The purpose of this study was to evaluate the effects of early administration and removal of the ACE inhibitor, captopril (CAP) on the plasma ACE activity, AVP levels, and mean arterial pressure (MAP) in groups of rats, control and CAP treated SHR and WKY (SHR, WKY SHRCAP, WKYCAP, respectively and in SHR taken off CAP (OFFCAP) and their progeny (2nd generation, 2ndG). Plasma ACE activity in SHRCAP (54.8 +/- 2.1 mU/ml/min) was significantly greater than in SHR (25.96 +/- 0.34 mU/ml/min) and their offspring (OFFCAP, 26.32 +/- 2.71 and 2ndG, 17.62 +/- 2.47 mU/ml/min, P < 0.001, respectively). Plasma level of AVP in SHR (14.18 +/- 0.98 pg/ml) were greater than in SHRCAP (9.1 +/- 1.01 pg/ml, P < 0.01). A decrease in plasma AVP levels were also noted in OFFCAP (10.48 +/- 0.51 pg/ml) and their offspring 2ndG (10.34 +/- 0.46 pg/ml). Our results did not show a relationship between plasma ACE activity and blood pressure reduction. However, treatment of SHR with captopril produced a decrease in plasma AVP levels which may participate in its antihypertensive mechanism of action.

Attenuated blood pressure responsiveness during post-exercise hypotension.

Abstract: Objective: To test the hypotheses that acute treadmill exercise would produce post-exercise hypotension (PEH) and that PEH would be associated with reduced mean arterial pressure (MAP) responsiveness to the α1-adrenergic agonist phenylephrine.Methods: Arterial and venous catheters were implanted into exercise-trained female Dahl-salt sensitive rats (n=9) for measurement of pulsatile blood pressure (BP) and heart rate (HR). The changes in BP following ganglionic blockade (hexamethonium/atropine) and the MAP responses to phenylephrine (PE) injections after ganglionic blockade (GB) were examined on separate days in testing cages (control) and following 40 min of treadmill exercise (post-ex).Results: Thirty minutes following graded treadmill exercise (20-40 m/min, 0% grade, 40 min duration) blood pressure was significantly reduced (-9 ± 1) mmHg compared to control. After exercise, GB produced a 43 ± 3 mmHg decrease in BP which tended (p=0.08) to be less than the reduction observed during control studies (51 ±...

ACE inhibition decreases postoperative mortality in rats with left ventricular hypertrophy and myocardial infarction.

Abstract: In male Sprague Dawley rats with left ventricular hypertrophy (LVH) and hypertension induced by aortic constriction (AC) and subsequent myocardial infarction (MI) by occlusion of the left coronary artery the effects of ACE inhibition with ramipril (RA 1 mg/kg/day via the drinking water during 6 weeks) on survival as well as cardiac function and metabolism were investigated. Respective groups (sham AC; AC; AC + sham MI; normotensive animals with sham MI; MI; MI+RA) served as comparisons.Conclusions: Hypertensive rats with LVH undergoing MI experienced increased postoperative mortality probably due to a reduced tolerance to myocardial ischemia and occurrence of arrhythmias. In these animals ACE inhibition with ramipril increased survival. Both, increased survival in hypertensive and reduction in infarct size in normotensive rats by ACE inhibition with ramipril was accompanied by an improved myocardial metabolism.Following MI hypertensive rats with AC and LVH revealed an increased postoperative mortality (68...

Natriuretic peptides in sheep with pressure overload left ventricular hypertrophy.

Abstract: To examine tissue and plasma atrial (ANP) and brain natriuretic peptide (BNP) responses to left ventricular hypertrophy (LVH) 7 sheep underwent suprarenal aortic banding (20 mmHg initial pressure differential). Median survival time was 15 days. Proximal mean aortic pressure (MAP) increased from 65.1 +/- 5.0 mmHg (baseline) to 111.6 +/- 7.5 mmHg (day 7, p < 0.0001). Distal systolic aortic pressure fell from 85.5 +/- 8.7 mmHg (baseline) to 55.6 +/- 6.4 mmHg (day 7, p = 0.0002). Maximal plasma ANP (26.9 +/- 3.6 vs 10.1 +/- 1.2 pmol/L, p = 0.005) and BNP (15.3 +/- 3.6 vs. 3.5 +/- 1.0 pmol/L, p = 0.006) were recorded at 15 +/- 4.0 days. Coarctation induced rapid increases in PRA and plasma aldosterone and a fall in urinary sodium. Post-mortem examination of hearts confirmed LVH. Compared with controls, tissue ANP concentration was reduced in left atrium (p = 0.04) and LV (p = 0.04). BNP concentration was reduced in left atrium (p = 0.02) but tended to be higher in LV. In conclusion, suprarenal aortic coarctation leads to progressive hypertension resulting in LVH, progressive increases in plasma ANP and BNP and, in most cases, death from heart failure.

Effect of losartan on right ventricular hypertrophy and cardiac angiotensin I-converting enzyme activity in pulmonary hypertensive rats.

Abstract: The aim of this study was to investigate the effect of prophylactic treatment with the angiotensin type 1 (AT1) receptor antagonist losartan on right ventricular hypertrophy and cardiac angiotensin 1-converting enzyme (ACE) activity in a rat model of monocrotaline-induced pulmonary hypertension. Losartan failed to prevent either pulmonary hypertension or right ventricular hypertrophy. Right ventricular ACE in untreated pulmonary hypertensive rats did not differ from control rats. Losartan treatment in pulmonary hypertensive rats caused a significant 2-fold increase of ACE activity in the hypertrophied right (p < 0.005) but not in the left ventricle. Thus, cardiac ACE activity is not stimulated in rats with monocrotaline-induced right ventricular hypertrophy. Prophylactic losartan treatment in this model of progressive pulmonary hypertension failed to prevent or reduce the increase in ventricular afterload. The relevance of the increase in right ventricular ACE activity during pulmonary hypertension after losartan treatment is unknown and needs to be evaluated in further studies.

The Mechanisms of the Improvement of Insulin Sensitivity by Angiotensin Converting Enzyme Inhibitor

Abstract: To investigate the role of kinins in augmentation of insulin sensitivity by angiotensin converting enzyme inhibitor (ACEI), the effects of ACEI (delapril) on the insulin resistance in fructose-fed rats (FFR) were evaluated with or without the administration of bradykinin receptor antagonist (Hoe 140). Male Sprague-Dawley rats were fed on fructose rich chow (FFR) or standard chow (control) for 4 weeks and treated with 10 mg/kg/day of delapril with or without Hoe 140 (0.5 mg/kg/day) for an additional 2 weeks. Steady state plasma glucose (SSPG) and steady state plasma insulin (SSPI) were determined while the rats were conscious. Insulin (2.5 mU/kg/min) and glucose (8 mg/kg/min) were simultaneously infused to determine insulin sensitivity in each group. Mean blood pressure (MBP), SSPG and SSPI were significantly higher in FFR than in control, and were significantly lower in the FFR+delapril than in FFR+vehicle. There were no difference in MBP, SSPG and SSPI between FFR+delapril+vehicle and FFR+delapril+Hoe 140. We concluded that the main mechanisms of improving the insulin sensitivity by ACEI may not be the enhancement of kinins but the suppression of angiotensin II in FFR.

Plasma endothelin-1 levels in patients with aldosterone-producing adenoma and pheochromocytoma.

Abstract: The aim of the study was to evaluate possible changes of plasma endothelin-1 levels (ET-1) in patients with hypertension secondary to primary aldosteronism and pheochromocytoma. We enrolled in the study: 12 patients affected by aldosterone-producing adenoma (5 M and 7 W; mean age 42.1 ± 17.2 years); 8 patients with pheochromocytoma (5 M, 3 W; mean age 36.2 ± 17.1 years); 15 patients with essential hypertension (9 M, 6 W; mean age 48.5±10 years). We also enrolled a normal control group (8 M, 12 W; mean age 34.2 ± 11 years). The mean plasma ET-1 concentrations in patients with pheochromocytoma were significantly higher (23.9 ± 5.2 pg/ml) than those in normal subjects (7.3 ± 1.9 pg/ml), in patients with primary aldosteronism (12.1 ± 3.8 pg/ml) and in patients with essential hypertension (9.2 ± 3 pg/ml); p < 0.001, respectively. The present investigation demonstrates that in human adrenal hypertension patients with pheochromocytoma have increased circulating ET-1 levels respect to patients with aldosterone-pr...

Cost-Effectiveness of Hypertension Treatment

Abstract: The benefits of antihypertensive treatment are influenced by both the absolute initial cardiovascular risk, and the relative reduction. Because age is a major determinant of the absolute cardiovascular risk, and because the strategies for hypertension diagnosis and treatment are not very much influenced by age, hypertension management appears to be more cost-effective after the age of 45, in both men and women. Below this age, the absolute gain in life-years seems to be smaller, and sensitivity analysis demonstrate an important influence on the results of assumptions about the effects of treatment on quality of life and the discounting rate.