Showing papers in "Hypertension in 1995"

Prevalence of Hypertension in the US Adult Population: Results From the Third National Health and Nutrition Examination Survey, 1988-1991

Abstract: The purpose of this study was to estimate the current prevalence and distribution of hypertension and to determine the status of hypertension awareness, treatment, and control in the US adult population. The study used a cross-sectional survey of the civilian, noninstitutionalized population of the United States, including an in-home interview and a clinic examination, each of which included measurement of blood pressure. Data for 9901 participants 18 years of age and older from phase 1 of the third National Health and Nutrition Examination Survey, collected from 1988 through 1991, were used. Twenty-four percent of the US adult population representing 43 186 000 persons had hypertension. The age-adjusted prevalence in the non-Hispanic black, non-Hispanic white, and Mexican American populations was 32.4%, 23.3%, and 22.6%, respectively. Overall, two thirds of the population with hypertension were aware of their diagnosis (69%), and a majority were taking prescribed medication (53%). Only one third of Mexican Americans with hypertension were being treated (35%), and only 14% achieved control in contrast to 25% and 24% of the non-Hispanic black and non-Hispanic white populations with hypertension, respectively. Almost 13 million adults classified as being normotensive reported being told on one or more occasions that they had hypertension; 51% of this group reported current adherence to lifestyle changes to control their hypertension. Hypertension continues to be a common finding in the general population. Awareness, treatment, and control of hypertension have improved substantially since the 1976-1980 National Health and Nutrition Examination Survey but continue to be suboptimal, especially in Mexican Americans. Consideration should be given to revision of the criteria for classification of hypertension to reflect the widespread use of lifestyle modification for treatment of hypertension.

Assessment of Arterial Distensibility by Automatic Pulse Wave Velocity Measurement: Validation and Clinical Application Studies

Abstract: Pulse wave velocity is widely used as an index of arterial distensibility. The aim of this study was to evaluate the accuracy of a new automatic device to measure it and then to analyze the major determinants of pulse wave velocity by application of this device in a large population. We evaluated the accuracy of on-line and computerized measurement of pulse wave velocity using an algorithm based on the time-shifted and repeated linear correlation calculation between the initial rise in pressure waveforms compared with the reference method (manual calculation) in 56 subjects. The results, analyzed according to the recommendations of Bland and Altman, showed a mean difference of -0.20 +/- 0.45 m/s for the mean carotid-femoral pulse wave velocity values (reference method, 11.05 +/- 2.58 m/s; automatic device, 10.85 +/- 2.44 m/s). The interreproducibility and intrareproducibility of measurements by each method were analyzed with the use of the repeatability coefficient according to the British Standards Institution. The interobserver repeatability coefficient was 0.947 for the manual method and 0.890 for the automatic, and intraobserver repeatability coefficients were 0.938 and 0.935, respectively. We evaluated the major determinants of the carotid-femoral pulse wave velocity measured by the automatic method in a separate study performed in 418 subjects of both sexes without any cardiovascular treatment or complication (18 to 77 years of age; 98 to 222 mm Hg systolic and 62 to 130 mm Hg diastolic pressure).(ABSTRACT TRUNCATED AT 250 WORDS)

Trends in the Prevalence, Awareness, Treatment, and Control of Hypertension in the Adult US Population: Data From the Health Examination Surveys, 1960 to 1991

Abstract: The objective of this study was to describe secular trends in the distribution of blood pressure and prevalence of hypertension in US adults and changes in rates of awareness, treatment, and control of hypertension. The study design comprised nationally representative cross-sectional surveys with both an in-person interview and a medical examination that included blood pressure measurement. Between 6530 and 13,645 adults, aged 18 through 74 years, were examined in each of four separate national surveys during 1960-1962, 1971-1974, 1976-1980, and 1988-1991. Protocols for blood pressure measurement varied significantly across the surveys and are presented in detail. Between the first (1971-1974) and second (1976-1980) National Health and Nutrition Examination Surveys (NHANES I and NHANES II, respectively), age-adjusted prevalence of hypertension at > or = 160/95 mm Hg remained stable at approximately 20%. In NHANES III (1988-1991), it was 14.2%. Age-adjusted prevalence at > or = 140/90 mm Hg peaked at 36.3% in NHANES I and declined to 20.4% in NHANES III. Age-specific prevalence rates have decreased for every age-sex-race subgroup except for black men aged 50 and older. Age-adjusted mean systolic pressures declined progressively from 131 mm Hg at the NHANES I examination to 119 mm Hg at the NHANES III examination. The mean systolic and diastolic pressures of every sex-race subgroup declined between NHANES II and III (3 to 6 mm Hg systolic, 6 to 9 mm Hg diastolic). During the interval between NHANES II and III, the threshold for defining hypertension was changed from 160/95 to 140/90 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

Spectral Analysis of Blood Pressure and Heart Rate Variability in Evaluating Cardiovascular Regulation A Critical Appraisal

Abstract: Blood pressure variability includes rhythmic and nonrhythmic fluctuations that, with the use of spectral analysis, appear as clear peaks or broadband power, respectively. This review offer...

Hypertension and the Pathogenesis of Atherosclerosis: Oxidative Stress and the Mediation of Arterial Inflammatory Response: A New Perspective

Abstract: Hypertension is a risk factor for the development of atherosclerosis, although the mechanisms have not been well elucidated. As the cellular and molecular mechanisms of the pathogenesis of atherosclerosis and the effects of hypertension are being more clearly defined, it becomes apparent that the two processes have certain common mechanisms. The endothelium is a likely central focus for the effect of both diseases. There is increasing evidence that atherosclerosis should be viewed fundamentally as an inflammatory disease. Atherogenic stimuli such as hyperlipidemia appear to active the inflammatory response by causing expression of mononuclear leukocyte recruiting mechanisms. The gene for one of these, the vascular cell adhesion molecule-1, is controlled at least in part by transcriptional factors regulated by oxidative stress, which modifies the redox state of the endothelial cell. Alterations in the redox state of the arterial wall also may contribute to vascular smooth muscle cell growth. In a somewhat parallel fashion, there is evidence that hypertension may also exert oxidative stress on the arterial wall. This article reviews evidence that leads to the postulate that hypertension predisposes to and accelerates atherosclerosis at least in part because of synergy between elevated blood pressure and other atherogenic stimuli to induce oxidative stress on the arterial wall.

Sympathetic activation in obese normotensive subjects

Abstract: Human obesity is characterized by profound alterations in the hemodynamic and metabolic states. Whether these alterations involve sympathetic drive is controversial. In 10 young obese subj...

A Noninvasive Computerized Tail-Cuff System for Measuring Blood Pressure in Mice

Abstract: We have validated a noninvasive computerized tail-cuff system for measuring blood pressure in mice. The system was designed to perform all functions automatically, including a programmable routine of cuff inflation and deflation, analysis and assignment of pulse rate and blood pressure, and recording of data electronically. To evaluate this system over a range of blood pressures, we gave groups of mice enalapril or N G -nitro-l-arginine methyl ester in their drinking water. For each of these groups, an equal number of control mice were given nothing in their drinking water. Tail-cuff blood pressures were recorded as the means of blood pressures determined on at least 3 days after at least 7 days of training. Tail-cuff enalapril and control group means were measured both 3 and 4 months after enalapril (or no drug) was begun; the group means at 3 months were not significantly different from the group means at 4 months. These results demonstrate that the system gives reproducible results. After the tail-cuff measurements were completed, intra-arterial blood pressures were attempted in all mice under unrestrained, unanesthetized conditions, and individual mouse (n=22) blood pressures with the use of the two methods were compared. The blood pressures from individual mice by tail-cuff and intra-arterial methods were highly correlated ( r =.86, P r =.98, P

Noninvasive Pulse Wave Analysis for the Early Detection of Vascular Disease

Abstract: A noninvasive technique has been developed and validated for calculating capacitive and oscillatory systemic arterial compliance with the use of pulse wave analysis and a modified Windkessel model. Application of the technique to subjects with hypertension, postmenopausal women with symptomatic coronary artery disease, and appropriate control subjects has confirmed a reduction of oscillatory compliance in the disease states and an increase in capacitive and oscillatory compliances in response to vasodilator drugs. This method should be useful in screening subjects for early evidence of vascular disease and in monitoring the response to therapy.

Diabetes mellitus and associated hypertension, vascular disease, and nephropathy : an update

Abstract: Because considerable important information has been published since our previous review, this update concentrates on new findings with regard to cardiovascular and renal risk factors contributing to the striking morbidity and mortality of these coexisting diseases. For example, a large body of investigative data has recently emerged suggesting or delineating a pathogenic role for hyperglycemic-related glycosylation and oxidation of lipoproteins and vascular and renal tissues. Great strides have recently been made in the understanding of platelet, coagulation, lipoprotein, and endothelial abnormalities in the pathogenesis of cardiovascular and renal disease associated with diabetes mellitus and hypertension. Major progress has been made in clarifying the pathophysiology of glomerulosclerosis and other processes involved in the progression of diabetic nephropathy. Furthermore, accumulating data surveyed in this review address new and promising pharmacological interventions that specifically address these pathophysiological mechanisms.

Increased Prevalence of Hypertension and Long-term Arsenic Exposure

Abstract: To examine the association between long-term exposure to inorganic arsenic and the prevalence of hypertension, we studied a total of 382 men and 516 women residing in villages where arseniasis was hyperendemic. Hypertension was defined as a systolic blood pressure of 160 mm Hg or greater, a diastolic blood pressure of 95 mm Hg or greater, or a history of hypertension treated regularly with antihypertensive drugs. The long-term arsenic exposure was calculated from the history of artesian well water consumption obtained through standardized interviews based on a structured questionnaire and the measured arsenic concentration in well water. Residents in villages where long-term arseniasis was hyperendemic had a 1.5-fold increase in age- and sex-adjusted prevalence of hypertension compared with residents in nonendemic areas. Duration of artesian well water consumption, average arsenic concentration in drinking water, and cumulative arsenic exposure were all significantly associated with hypertension prevalence. The higher the cumulative arsenic exposure, the higher the prevalence of hypertension. This dose-response relation remained significant after adjustment for age, sex, diabetes mellitus, proteinuria, body mass index, and serum triglyceride level. The results suggest that long-term arsenic exposure may induce hypertension in humans.

Renal Afferent Denervation Prevents Hypertension in Rats With Chronic Renal Failure

Abstract: Increased activity of the sympathetic nervous system has been described in chronic renal failure, but its role in the genesis and maintenance of hypertension associated with this condition has not been established. The kidney has an intense network of chemoreceptors and baroreceptors that send impulses to the brain. To what extent activation of these receptors by the scarred kidney or the uremic milieu may contribute to this model of hypertension is unknown. In the present study, we evaluated the effect of bilateral dorsal rhizotomy on the development of hypertension and neuroadrenergic activity in the anterior, lateral, and posterior hypothalamic nuclei, in the locus ceruleus, and in the nucleus tractus solitarius of Sprague-Dawley rats that underwent 5/6 nephrectomy or were sham operated. Neuroadrenergic activity was determined by calculating norepinephrine turnover rate after inhibition of norepinephrine synthesis with α-methyl-dl- p -tyrosine methyl ester hydrochloride. The endogenous norepinephrine concentration was significantly greater in the posterior and lateral hypothalamic nuclei and the locus ceruleus, but not in the nucleus tractus solitarius, and the anterior hypothalamic nuclei of uremic rats compared with control rats. In rats with chronic renal failure and sham rhizotomy, the turnover rate of norepinephrine in the posterior (15.3±1.61 nmol · g −1 · h −1 ) and lateral hypothalamic nuclei (11.7±2.12 nmol · g −1 · h −1 ) and in the locus ceruleus (26.6±2.42 nmol · g −1 · h −1 ) was significantly faster ( P −1 · h −1 , respectively) or control animals with or without rhizotomy. The turnover rate of norepinephrine in the anterior hypothalamic nuclei and the nucleus tractus solitarius was not different among the three groups of rats. These studies demonstrated that in rats with chronic renal failure, bilateral dorsal rhizotomy in the dorsolateral aspect of the vertebral bodies (T10 to L2) prevents in large part the development of hypertension and the increase in norepinephrine turnover rate in the posterior and lateral hypothalamic nuclei and the locus ceruleus. The data provide evidence that renal afferent impulses from the kidneys of rats with chronic renal failure may activate areas of the brain involved in the neuroadrenergic regulation of blood pressure. This mechanism may contribute to the genesis of hypertension in uremic rats.

Measuring Forearm Blood Flow and Interpreting the Responses to Drugs and Mediators

Abstract: Venous occlusion plethysmography has been widely used to study forearm blood flow. The principle of the technique is straightforward: the rate of swelling of the forearm during occlusion o...

Spontaneous Cardiac Baroreflex in Humans: Comparison With Drug-Induced Responses

Abstract: We compared two methods of assessment of baroreflex sensitivity in eight supine healthy volunteers during repeated baseline measurements and various conditions of cardiac autonomic blockade. The spontaneous baroreflex method involved computer scanning of recordings of continuous finger arterial pressure and electrocardiogram to locate sequences of three or more beats in which pressure spontaneously increased or decreased, with parallel changes in pulse intervals. The mean regression slope of all these sequences during each study condition was considered to represent the mean spontaneous baroreflex slope. In the drug-induced method, sigmoidal curves were constructed from data obtained by bolus injections of phenylephrine and nitroprusside; the tangents taken at the resting pressure of each of these curves were compared with the mean spontaneous baroreflex slopes. The two methods yielded slopes that were highly correlated (r = .96, P < .001), with significant but similar intraindividual baseline variability. Atropine virtually eliminated the baroreflex slope; subsequent addition of propranolol did not alter it further. Propranolol or clonidine alone increased average baroreflex slope to the extent that they increased resting pulse interval (r = .69 to .83). The spontaneous baroreflex method provides a reliable, noninvasive assessment of human vagal cardiac baroreflex sensitivity within its physiological operating range.

Mechanical Principles in Arterial Disease

Abstract: Arterial disease and degeneration are the major causes of cardiovascular death and disability, including myocardial and cerebral infarction, cerebral hemorrhage, and hypertensive left ventricular failure. Recent research has concentrated on chemical and molecular mechanisms: on thrombogenesis and thrombolysis, vasoactive chemicals produced by endothelial cells, and the chemical control of cardiac and vascular remodeling. There has been far less concern with details of physical factors and their relevance to atherogenesis, plaque rupture, aortic medial degeneration, and altered left ventricular hydraulic load. This is a serious anomaly, since the functions of the heart and arteries are mechanical rather than chemical: those of the heart is to contract and to generate flow; those of the arteries is to transmit blood and to cushion pulsations. Their diseases and resultant complications are mechanical as well, comprising arterial obstruction, arterial rupture, and failure of the heart as a mechanical pump. A logical approach to therapy requires consideration of mechanics and physical principles in sufficient detail to explain observed phenomena. Such an approach to arterial disease is not the role of the surgeon alone but should be taken by contemporary internists, cardiologists, and specialists in hypertensive disease. Practicing physicians need to look beyond simplistic mechanical notions and beyond simple instruments such as the cuff sphygmomanometer, which still dominates clinical practice as it has for the past 100 years. It is appropriate that they consider those recent advances in mechanical science that are as important and as far-reaching as those in chemical and molecular science but that have not yet been widely applied to assessment of cardiovascular function and disease. This symposium deals with some of these advances. The title of this symposium, the “Second Workshop on Structure and Function of Large Arteries,” is similar to another arranged by the American Heart Association on “Functional and Structural Aspects …

Renal denervation attenuates the sodium retention and hypertension associated with obesity

Abstract: Recent studies have indicated that obesity is associated with hypertension, sodium retention, and increased sympathetic nervous system activity. The purpose of this study was to determine the role of renal nerves in mediating the sodium retention and hypertension associated with obesity. We determined the hemodynamic and renal excretory responses to a high-fat diet in control (n=6) and bilaterally renal-denervated (n=7) chronically instrumented dogs. After a control period of 8 days, dogs were placed on a high-fat diet for 5 weeks. In response to a high-fat diet, body weight increased from 19.9±2.2 to 29.9±2.4 kg in the control group and from 21.1±2.0 to 32.4±1.9 kg in the bilaterally renal-denervated group. Heart rate increased from 81±8 to 113±7 beats per minute in the control group and from 79±7 to 103±8 beats per minute in the bilaterally renal-denervated group. Arterial pressure increased significantly from 95±2 to 109±4 mm Hg in the control group. In contrast, 5 weeks of a high-fat diet in the bilaterally renal-denervated group did not significantly increase arterial pressure (which went from 87±3 to 90±4 mm Hg). Furthermore, the decrease in sodium excretion in response to the high-fat diet was significantly greater in the control group than in the bilaterally renal-denervated group. After 5 weeks of a high-fat diet, cumulative sodium retention was 455±85 mmol in the control group and only 252±47 mmol in the bilaterally renal-denervated group. Similar increases in glomerular filtration rate and renal plasma flow occurred in both groups in response to the high-fat diet. The results of this study indicate that the renal nerves play an important role in mediating the sodium retention and hypertension associated with obesity in dogs.

In vivo evidence for microvascular oxidative stress in spontaneously hypertensive rats. Hydroethidine microfluorography.

Abstract: The factors that predispose to the accelerated organ injury that accompanies the hypertensive syndrome have remained speculative and without a firm experimental basis. Indirect evidence has suggested that a key feature may be related to an enhanced oxygen radical production. The purpose of this study was to refine and use a technique to visualize evidence of spontaneous microvascular oxidative stress in vivo in the spontaneously hypertensive rat (SHR) compared with its normotensive control, the Wistar-Kyoto rat (WKY). We investigated the effects of adrenal glucocorticoids on the microvascular oxidative stress sequence. The mesentery was superfused with hydroethidine, a reduced, nonfluorescent precursor of ethidium bromide. In the presence of oxidative challenge, hydroethidine is transformed intracellularly into the fluorescent compound ethidium bromide, which binds to DNA and can be detected by virtue of its red fluorescence. The fluorescent light emission from freshly exteriorized and otherwise unstimulated mesentery microvessels was recorded by digital microscopy. The number of ethidium bromide–positive nuclei along the arteriolar and venular walls in SHR was found to be significantly increased above the level exhibited by WKY. The elevation in ethidium bromide fluorescence in SHR arterioles could be attenuated by a synthetic glucocorticoid inhibitor and in rats subjected to adrenalectomy. The administration of glucocorticoids after adrenalectomy by injection of dexamethasone restored the oxidative reaction in SHR arterioles. Treatment with dimethylthiourea and with a xanthine oxidase inhibitor attenuated the superoxide formation. Although a nitric oxide synthase inhibitor ( N G -nitro-l-arginine methyl ester) enhanced the ethidium bromide staining in WKY, it did not affect that in SHR. Our findings suggest an enhancement of spontaneous oxidative stress in the microvascular wall of SHR that appears to be associated with glucocorticoid synthesis.

Early Predictors of 15-Year End-Stage Renal Disease in Hypertensive Patients

Abstract: There has been a continuing increase in the incidence of end-stage renal disease (ESRD) in the United States, including the fraction that has been attributed to hypertension. This study was done to seek relationships between ESRD and pretreatment clinical data and between ESRD and early treated blood pressure data in a population of hypertensive veterans. We identified a total of 5730 black and 6182 nonblack male veterans as hypertensive from 1974 through 1976 in 32 Veterans Administration Hypertension Screening and Treatment Program clinics. Their mean age was 52.5±10.2 years, and their mean pretreatment blood pressure was 154.3±19.0/100.8±9.8 mm Hg. During a minimum of 13.9 years of follow-up, 5337 (44.8%) of these patients died and 245 developed ESRD. For 1055 of these subjects, pretreatment systolic blood pressure (SBP) was greater than 180 mm Hg; 901 were diabetic; 1471 had a history of urinary tract problems; and 2358 of the 9644 who were treated had an early fall in SBP of more than 20 mm Hg. We used proportional hazards modeling to fit multivariate survival models to determine the effect of the available pretreatment data and early treated blood pressure levels on ESRD. This model demonstrated the independent increased risk of ESRD associated with being black or diabetic (risk ratio, 2.2 or 1.8), having a history of urinary tract problems (risk ratio, 2.2), or having high pretreatment SBP (for SBP 165 to 180 mm Hg, risk ratio was 2.8; for SBP >180 mm Hg, risk ratio was 7.6). In addition, myocardial infarction during follow-up increased the risk of subsequent ESRD almost twofold, and congestive heart failure increased it more than fivefold. The rate of ESRD in those whose SBP fell more than 20 mm Hg decreased by two thirds.

Combined renal effects of overweight and hypertension.

Abstract: The existence of a direct relationship between body mass and arterial pressure is well recognized; however, the effect of obesity on known target organs of hypertension is not clearly understood. We undertook the present studies to assess the influence of obesity on renal function and urinary albumin excretion in 40 normotensive subjects and 80 never-treated hypertensive patients matched for age, sex, arterial pressure level, and known duration of hypertension in whom an oral glucose tolerance test was within normal limits. Glomerular filtration rate and effective renal plasma flow (expressed as absolute values or values normalized for height) were increased in overweight compared with lean subjects whether normotensive or hypertensive. Glomerular filtration rate was positively correlated with protein intake (as assessed from urinary excretion of urea) and fasting serum insulin level. Urinary excretion of albumin but not IgG and β 2 microglobulin was higher in hypertensive patients compared with normotensive subjects. The overweight condition clearly enhanced the influence of arterial pressure on albuminuria; in fact, a steeper regression line between albumin excretion rate and arterial pressure was found in overweight compared with lean subjects. These results indicate that the overweight condition is associated with renal hyperfiltration and hyperperfusion, irrespective of the presence of hypertension, and that obesity magnifies the effect of hypertension on albuminuria, thus raising the possibility of an increased susceptibility of obese hypertensive patients to the development of renal damage.

A Randomized Controlled Trial of Stress Reduction for Hypertension in Older African Americans

Abstract: We tested the short-term efficacy and feasibility of two stress education approaches toe the treatment of mild hypertension in older African Americans. This was a randomized, controlled, single-blind trial with 3 months of follow-up in primary care, inner-city health center. Of 213 African American men and women screened, 127 individuals (aged 55 to 85 years with initial diastolic pressure of 90 to 109 mm Hg, systolic pressure of < or = 189 mm Hg, and final baseline blood pressure of < or = 179/104 mm Hg) were selected. Of these, 16 did not complete follow-up blood pressure measurements. Mental and physical stress reduction approaches (Transcendental Meditation and progressive muscle relaxation) were compared with a lifestyle modification education control program and with each other. The primary outcome measures were changes in clinic diastolic and systolic pressures from baseline to final follow-up, measured by blinded observers. The secondary measures were linear blood pressure trends, changes in home blood pressure, and intervention compliance. Adjusted for significant baseline differences and compared with control, Transcendental Meditation reduced systolic pressure by 10.7 mm Hg (P < .0003) and diastolic pressure by 6.4 mm Hg (P <.00005). Progressive muscle relaxation lowered systolic pressure by 4.7 mm Hg (P = 0054) and diastolic pressure by 3.3 mm Hg (P <.02). The reductions in the Transcendental Meditation group were significantly greater than in the progressive muscle relaxation group for both systolic blood pressure (P = .02) and diastolic blood pressure (P = .03). Linear trend analysis confirmed these patterns.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of Superoxide in the Depressed Nitric Oxide Production by the Endothelium of Genetically Hypertensive Rats

Abstract: We undertook these studies to determine whether a deficient nitric oxide production in genetically hypertensive rats could result from its being scavenged by an excess production of superoxide. In one study we used a porphyrinic microsensor to measure nitric oxide concentrations released by cultured endothelial cells from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY). SHRSP cells released only about one third the concentration of nitric oxide as did WKY cells. Treatment of cells with superoxide dismutase increased nitric oxide release, demonstrating that normally nitric oxide is scavenged by endogenous superoxide. The increase in nitric oxide release in response to superoxide dismutase treatment was more than twice as great from SHRSP as from WKY cells, demonstrating the greater amount of superoxide in the hypertensive rats. A direct measure of superoxide with the use of lucigenin demonstrated the presence of 68.1 +/- 7.1 and 27.4 +/- 3.5 nmol/L of this anion in SHRSP and WKY endothelial cells, respectively. The presence of superoxide in the rat aorta was also estimated by quantification of its effect on carbachol relaxation. This relaxation was diminished when endogenous superoxide dismutase was blocked by diethyldithiocarbamic acid. This blockade reduced the relaxation by 51.2 +/- 5.2% in SHRSP aortas and by only 22.0 +/- 8.2% (P = .015) in WKY aortas. Data from these diverse systems are in agreement that superoxide production is excessive in SHRSP tissues. This excess superoxide, by scavenging endothelial nitric oxide, could contribute to the increased vascular smooth muscle contraction and hence to the elevated total peripheral resistance of these rats.

Effect of Antihypertensive Treatment on Small Arteries of Patients With Previously Untreated Essential Hypertension

Abstract: In a double-blind randomized trial, the effects of treatment with an angiotensin-converting enzyme (ACE) inhibitor (perindopril) and a beta-blocker (atenolol) on small artery structure were compared in previously untreated essential hypertensive patients. Subjects (diastolic blood pressure > or = 100 and < or = 120 mm Hg) were randomly assigned to treatment for 12 months with either perindopril (n = 13, 4 to 8 mg/d) or atenolol (n = 12, 50 to 100 mg/d); the dosage was adjusted upward and in some cases combined (n = 5, perindopril; n = 2, atenolol) with thiazide diuretic to achieve target blood pressure (diastolic blood pressure below 90 mm Hg). Before and at the end of treatment, gluteal biopsies were taken under local anesthetic; from these biopsies, two small arteries were dissected and mounted on a myograph for morphometry. The reduction in blood pressure with atenolol (drop in mean blood pressure 28.4 +/- 1.8 mm Hg) was greater than with perindopril (20.6 +/- 1.8 mm Hg, P < .05). Perindopril treatment caused an increase in small artery diameter (231 +/- 14 to 274 +/- 13 microns, P < .05) and a reduction in the ratio of media thickness to lumen diameter (7.94 +/- 0.65% to 5.96 +/- 0.42%, P < .05), whereas atenolol had no effect (246 +/- 14 to 231 +/- 13 microns and 7.14 +/- 0.47% to 6.79 +/- 0.45%, respectively). The change in small artery morphology caused by perindopril was not accompanied by any change in media cross-sectional area, suggesting that the change was due to "remodeling."(ABSTRACT TRUNCATED AT 250 WORDS)

Low Urinary Sodium Is Associated With Greater Risk of Myocardial Infarction Among Treated Hypertensive Men

Abstract: A sodium-reduced diet is frequently recommended for hypertensive individuals. To determine the relationship of sodium intake to subsequent cardiovascular disease, we assessed the experience of participants in a worksite-based cohort of hypertensive subjects. The 24-hour urinary excretion of sodium (UNaV), potassium, creatinine, and plasma renin activity was measured in 2937 mildly and moderately hypertensive subjects who were unmedicated for at least 3-4 weeks. Morbidity and mortality in these systematically treated subjects were ascertained. Men and women were stratified according to sex-specific quartiles of UNaV. Subjects in these strata were similar in race, cardiovascular status, and pretreatment and intreatment blood pressure. Subjects with lower UNaV were thinner, excreted less potassium, and had higher plasma renin activity. During an average 3.8 years of follow-up, a total of 55 myocardial infarctions occurred. Myocardial infarction and UNaV were inversely associated in the total population and in men but not in women, who sustained only nine events. In men, age- and race-adjusted myocardial infarction incidence in the lowest versus highest UNaV quartile was 11.5 versus 2.5 (relative risk, 4.3, 95% confidence interval, 1.7-10.6). No association was observed between non-cardiovascular disease mortality (n = 11) and UNaV. There was a significant linear trend in proportions of myocardial infarction by UNaV quartile, with a break point after the lowest UNaV quartile.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II Increases Vascular Permeability Factor Gene Expression by Human Vascular Smooth Muscle Cells

Abstract: Angiotensin II (Ang II) has been implicated in the pathogenesis of the vascular injury associated with hypertension and diabetes mellitus. Increased vascular permeability is an important early manifestation of endothelial dysfunction and the pathogenesis of atherosclerosis. How Ang II contributes to endothelial dysfunction and promotes an increase in vascular permeability is unknown but is classically attributed to its pressor actions. We demonstrate that human vascular smooth muscle cells express abundant mRNA for vascular permeability/endothelial growth factor. Vascular permeability factor is a 34- to 42-kD glycoprotein that markedly increases vascular endothelial permeability and is a potent endothelial mitogen. Ang II potently induced a concentration-dependent (maximal, 10(-7) mol/L) and time-dependent increase in vascular permeability factor mRNA expression by human vascular smooth muscle cells that was maximal after 3 hours and diminished by 24 hours. Ang II-induced vascular permeability factor mRNA expression by human vascular smooth muscle cells was inhibited by the specific Ang II receptor antagonist losartan (DuP 753), confirming that this is an Ang II receptor subtype 1-mediated event. These results describe a new action of Ang II on human vascular smooth muscle, notably the induction of vascular permeability factor mRNA expression. The wide spectrum and potent activity of vascular permeability factor suggest a novel mechanism whereby Ang II could locally and directly influence the permeability, growth, and function of the vascular endothelium independent of changes in hemodynamics.

Natriuretic Peptides Inhibit DNA Synthesis in Cardiac Fibroblasts

Abstract: We have examined the effects of the natriuretic peptides on DNA synthesis in primary cultures of neonatal rat cardiac fibroblasts. Binding analysis using 125I-labeled atrial natriuretic peptide identified a single class of high-affinity binding sites (Kd = 0.03 +/- 0.01 nmol/L) in these cells. Of these sites, 80% appear to be of the natriuretic peptide C receptor subtype, with the remainder being A and B receptor subtypes. Northern blot analysis confirmed the presence of all three natriuretic peptide receptors in these cells. Atrial natriuretic peptide (10(-7) mol/L) effected a modest but consistent reduction in both agonist- and stretch-stimulated [3H]thymidine incorporation (17% to 41%). Moreover, brain natriuretic peptide (10(-7) mol/L), C-type natriuretic peptide (10(-7) mol/L), and des-[Gln18,Ser19,Gly20,Leu21,Gly22]-ANF 4-23-NH2 (10(-7) to 10(-6) mol/L) all proved capable of antagonizing growth factor-dependent [3H]thymidine incorporation (the inhibition ranged from 14% to 28%) and cell proliferation, suggesting that all three natriuretic peptide receptor subtypes are involved in the regulation of mitogenesis in these cultures. The inhibition by atrial natriuretic peptide was amplified by cotreatment with phosphodiesterase inhibitors. Similar reduction in [3H]thymidine incorporation was seen after treatment with 8-bromo-cGMP (10(-4) to 10(-3) mol/L) or nitroprusside (10(-4) to 10(-3) mol/L). These results suggest an important paracrine role for the natriuretic peptides in regulating fibroblast growth during cardiac hypertrophy.

Different mechanisms of endothelial dysfunction with aging and hypertension in rat aorta.

Abstract: We analyzed the effects and mechanisms of aging in aortic endothelium and vascular smooth muscle of 12-week-old (adult) and 72-week-old (senescent) normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Aortas were suspended in organ chambers filled with physiological salt solution (95% O 2 /5% CO 2 ; 37°C), and isometric tension was measured. In WKY, endothelium-dependent relaxations to acetylcholine were diminished with aging ( P P P N G -nitro-l-arginine methyl ester ( P P P =NS versus senescent WKY). The thromboxane analogue U46619 elicited similar contractions in adult and senescent WKY and adult SHR, whereas responses in senescent SHR were weaker ( P P P 2 , whereas in senescent SHR and senescent WKY, impaired formation or increased inactivation of nitric oxide must be involved. Contractions to endothelin but not to norepinephrine are reduced with aging only in SHR.

Influence of Blood Pressure on Left Atrial Size: The Framingham Heart Study

Abstract: Increased left atrial size has been identified as a precursor of atrial fibrillation and of stroke once atrial fibrillation is manifest. Conflicting data exist regarding the effect of high blood pressure on left atrial size. Our objective was to evaluate the association of contemporary and long-term measures of blood pressure with echocardiographically determined left atrial size in a large, population-based cohort. The study sample consisted of 1849 male and 2152 female participants of the Framingham Heart Study and Framingham Offspring Study. All analyses were sex specific. In correlation analyses, systolic and pulse pressures were identified as statistically significant determinants of left atrial size after adjustment for age and body mass index, although the magnitudes of these relations were very modest (partial r < or = .10). Multivariable linear regression models showed the relative contributions of the pressure variables to the prediction of left atrial size to be substantially less than those of age and, in particular, body mass index. Furthermore, inclusion of left ventricular mass in these multivariable models eliminated or attenuated the associations of the pressure variables with left atrial size. In logistic analyses, increasing levels of the pressure variables were significantly predictive of left atrial enlargement. Subjects with 8-year average systolic pressure of 140 mm Hg or higher were twice as likely to have left atrial enlargement as those with values of 110 mm Hg or lower. Overall, in this population-based study sample, increased levels of systolic and pulse pressures (but not diastolic or mean arterial pressures) were significantly associated with increased left atrial size.(ABSTRACT TRUNCATED AT 250 WORDS)

Autonomic Nervous Function in Non-dipper Essential Hypertensive Subjects: Evaluation by Power Spectral Analysis of Heart Rate Variability

Abstract: Autonomic nervous function was evaluated by means of power spectral analysis of heart rate variability in hospitalized dipper (n = 31) and non-dipper (n = 31) essential hypertensive subjects. Twenty-four-hour blood pressure (BP) measurement was performed by the cuff-oscillometric method to evaluate the nocturnal decrease of BP. The non-dipper subjects were defined as those whose nocturnal decrease of systolic BP was < 10% of daytime BP. Power spectral analysis of RR interval was performed from Holter ECG every 10 minutes by the maximum entropy method to obtain the low-frequency band (LFB, 0.04 to 0.15 Hz), which is an index of both parasympathetic and sympathetic nervous activities, and the high frequency band (HFB, 0.15 to 0.4 Hz), which reflects parasympathetic nervous activity. LFB and HFB were averaged every hour to obtain hourly LFB and HFB values. Total LFB and total HFB were calculated as the mean values of 24 hourly averaged LFBs and HFBs. Both LFB and HFB were significantly lower in non-dipper hypertensives than in dipper subjects throughout the day. In dipper hypertensives, LFB showed a nocturnal decrease, whereas HFB was significantly increased during the nighttime. However, these diurnal changes in LFB and HFB were significantly blunted in non-dipper subjects. These findings indicate that non-dipper hypertensive subjects were characterized with a decreased physiological circadian fluctuation on autonomic functions compared with dipper subjects. This alteration in the autonomic nervous function may explain the non-dipper phenomenon in essential hypertension.

Circulating Nitric Oxide (Nitrite/Nitrate) Levels in Postmenopausal Women Substituted With 17β-Estradiol and Norethisterone Acetate: A Two-Year Follow-up Study

Abstract: Postmenopausal women (PMW) have an increased risk of cardiovascular disease that is attenuated by hormone replacement therapy (HRT) Inasmuch as hypertension and atherosclerosis are associated with diminished endothelium-derived nitric oxide (NO), we investigated whether HRT augments NO release in PMW We determined serum levels of nitrite/nitrate (NO 2 +NO 3 ) at baseline and during the 6th, 12th, and 24th months of the study in two groups of PMW One group (HRT-PMW, n=13) received continuous transdermal administration of 17β-estradiol (Estraderm-TTS-50) supplemented with oral norethisterone acetate (NETA) on days 1 through 12 of each month, and the other group (control PMW, n=13) did not receive HRT Blood samples in the HRT-PMW group were collected without regard to whether subjects were taking NETA at the time of blood sampling Serum NO 2 +NO 3 levels increased in HRT-PMW for the duration of the study, whereas serum NO 2 +NO 3 levels remained unchanged in control PMW When all samples regardless of timing of collection with respect to NETA treatment were included in the statistical analysis, the change in NO 2 +NO 3 levels in HRT-PMW was significantly greater compared with the change in control PMW ( P =037) Likewise, when only those samples collected when estradiol-treated subjects were not taking oral NETA were included in the statistical analysis, the change in NO 2 +NO 3 levels in the HRT-PMW group remained significant ( P =047) compared with control PMW In contrast, when only those samples collected when estradiol-treated subjects were taking NETA were included in the analysis, the change in NO 2 +NO 3 levels in the HRT-PMW group was not significant ( P =23) compared with control PMW These results indicate that HRT increases NO levels in PMW, an effect that may contribute to the cardiovascular protection afforded by HRT in PMW In addition, our data suggest, but do not prove, that concomitant administration of a progestin may attenuate the beneficial effects of estrogen replacement therapy with regard to NO release

Coronary Kinin Generation Mediates Nitric Oxide Release After Angiotensin Receptor Stimulation

Abstract: Our goal was to determine whether angiotensin II (Ang II) and its metabolic fragments release nitric oxide and the mechanisms by which this occurs in blood vessels from the canine heart. We incubated 20 mg of microvessels or large coronary arteries in phosphate-buffered saline for 20 minutes and measured nitrite release. Nitrite release increased from 27±2 up to 103±5, 145±17, 84±4, 107±16, and 54±4 pmol/mg ( P −5 mol/L of Ang I, II, III, IV, and Ang-(1-7), respectively. The effects of all angiotensins were blocked by N ω -nitro-l-arginine methyl ester (100 μmol/L), indicating that nitrite was a product of nitric oxide metabolism, and by Hoe 140 (10 μmol/L), a specific bradykinin B 2 receptor antagonist, indicating a potential role for local kinin formation. The protease inhibitors aprotinin (10 μmol/L) and soybean trypsin inhibitor, which block local kinin formation, inhibited nitrite release by all of the angiotensins. Angiotensin nonselective (saralasin), type 1–specific (losartan), and type 2–specific (PD 123319) receptor antagonists abolished the nitrite released in response to all the fragments. Angiotensin type 1 and type 2 and receptors mediate nitrite release after Ang I, II, III, and Ang-(1-7), whereas only type 2 receptors mediate nitrite release after Ang IV. Similar results were obtained in large coronary arteries. In summary, formation of nitrite from coronary microvessels and large arteries in the normal dog heart in response to angiotensin peptides is due to the activation of local kinin production in the coronary vessel wall.

Apoptosis in Target Organs of Hypertension

Abstract: Apoptosis or programmed cell death frequently parallels abnormalities in cell proliferation and differentiation. As hypertrophy/hyperplasia or remodeling occurs in organs affected by hypertension, we evaluated the degree of apoptosis in the heart, kidney, and brain in situ in genetically hypertensive mice and rats as well as in cultured vascular smooth muscle cells. Apoptosis was characterized by morphological features, DNA fragmentation, and laddering as well as by terminal deoxynucleotidyl transferase labeling of the 3' OH ends of both extracted DNA and tissue sections. The present report provides the first evidence of increased apoptosis in whole organs of genetically hypertensive rat and mouse strains: in the heart of spontaneously hypertensive rats (SHR) and in the heart (ventricular cardiomyocytes), kidney (inner cortex and medulla), and brain (cortex, striatum, hippocampus, and thalamus) of spontaneously hypertensive mice, with a higher effect of apoptotic inducers in cultured aortic smooth muscle cells derived from SHR. Both types of known apoptotic processes, oligonucleosomal cleavage and large DNA fragmentation, were observed in vascular smooth muscle cells, but only the former appeared to be increased in SHR. This study underlines the importance of cell death dysregulation in hypertension, reveals a new route for investigation of the pathogenesis of hypertension, and suggests novel targets of therapeutic intervention.