Aram V. Chobanian

Antiatherogenic effect of captopril in the Watanabe heritable hyperlipidemic rabbit.

The effects of 9 months of orally administered captopril (25-50 mg/kg body wt/day) on aortic atherosclerosis was examined in normotensive Watanabe heritable hyperlipidemic rabbits. Captopril caused a significant decrease in aortic atherosclerosis. Total aortic surface involvement by lesions was reduced from 48 +/- 3.6% in control Watanabe rabbits to 30 +/- 3.9% with captopril treatment (p less than 0.01). Most of the decrease could be accounted for by a marked reduction in atherosclerosis of descending thoracic aortas from 49 +/- 5.2% to 15 +/- 3.9% in control and captopril-related groups, respectively (p less than 0.001). Significant decrease in cholesterol content of descending thoracic aorta was also observed in captopril-treated rabbits. Microscopic examination of the arterial lesions in captopril-treated animals suggested a relative decrease in cellularity and increase in extracellular matrix as compared with untreated animals. These studies indicate that captopril has a potent antiatherosclerotic action in the Watanabe heritable hyperlipidemic rabbit.

Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) Resetting the Hypertension Sails

The National High Blood Pressure Education Program (NHBPEP), coordinated by the National Heart, Lung, and Blood Institute (NHLBI), has released its long-awaited Joint National Committee (JNC) 7 report.1 The report will be made available in 2 forms: the “Express” or short version and a longer version that will be published in Hypertension and will provide more detail regarding the recommendations. On its surface, it resembles the 6 predecessors, but to fully appreciate this new landmark document, one must recognize the process and context from which it is derived and what it is about to do. You cannot direct the winds; you can adjust the sails. Approximately 35 years ago, clinicians were busy managing severe and malignant hypertension. Hospitals filled their beds with stroke patients and stroke wards were commonplace. Coronary heart disease and stroke prevalence and accompanying mortality rates were the highest ever recorded. During the next generation, different classes of antihypertensive agents were developed and tested in a variety of settings and among different patients. The studies independently and collectively contributed to a universal finding: lowering arterial pressure can remarkably reduce cardiovascular morbidity and mortality rates as well as slow the progression of renal disease, retinopathy, and all-cause deaths. When these findings first became available, the NHLBI formed the NHBPEP, designed to translate this information through public and professional education programs. …

The Hypertension Paradox — More Uncontrolled Disease despite Improved Therapy

In the 2009 Shattuck Lecture, Aram Chobanian describes the tremendous progress that has been made in the recognition and treatment of hypertension in the past 60 years. He lays out the basis of an apparent paradox: despite better recognition and treatment, the prevalence of untreated hypertension continues to increase.

National Heart, Lung, and Blood Institute Workshop on Sodium and Blood Pressure A Critical Review of Current Scientific Evidence

The Workshop on Sodium and Blood Pressure was convened by the National Heart, Lung, and Blood Institute (NHLBI) in Bethesda, Md, on January 28 and 29, 1999, to update earlier reviews of this topic.1 2 3 Other topics covered were sodium intake in relation to other cardiovascular disease (CVD) and non-CVD conditions, research needs, and public policy considerations. More than 55 invited speakers and other attendees from the United States and abroad reviewed and discussed the scientific information. This review synthesizes the presentations and discussions. Epidemiological studies conducted over the past 50 years have shown a clear curvilinear relation of higher adult blood pressure (BP) levels to higher rates of coronary heart disease (CHD), stroke, heart failure, and kidney failure. A continuous relation is apparent from below the 120/80 mm Hg level. Thus, a significant portion of CVD occurs in persons whose BP has not reached the arbitrary 140/90 mm Hg level defining hypertension. Studies show unequivocally that lowering high BP in hypertensive patients can reduce the likelihood of developing or dying from CVD, including CHD and stroke. Dietary factors in individuals and in the population at large have important effects on BP levels, which are generally assumed to translate to CVD risk. For the nonhypertensive subset, a population-wide approach to lowering BP (an approach based on lifestyle modifications that have been shown to prevent or delay increases in BP) could affect the total CVD burden as much as or more than treating only those with established hypertension. There is an abundance of scientific evidence demonstrating a direct relation between salt intake and BP. Studies in laboratory animals show that high BP can be induced by diet.4 Recent evidence comes from a randomized trial involving 26 chimpanzees that were given a low salt/high potassium diet (preintervention period). Subsequently, …

Angiotensin II induces fibronectin expression associated with cardiac fibrosis in the rat.

Fibronectin expression was studied in the heart of rats given a continuous infusion of angiotensin II (Ang II). Northern blot analysis showed that left ventricular fibronectin steady-state mRNA increased fivefold to eightfold in response to pressor doses of Ang II after 24 hours. Accumulation of immunodetectable fibronectin in the ventricles occurred after the mRNA levels increased. The changes in fibronectin expression were reversible when Ang II treatment was withdrawn. The Ang II-induced increase in fibronectin mRNA accompanied similar increases for collagen type I, collagen type IV, and atrial natriuretic factor steady-state mRNA. Interstitial and perivascular fibrosis was identified in both ventricles of angiotensin-treated rats within 3 days. In situ hybridization identified cells associated with areas of fibrosis as the principal site of fibronectin mRNA accumulation in treated animals. By comparison, normal hearts showed fibronectin expression primarily within ventricular vascular tissue and the atrial endocardium. A dose-dependent reduction of fibronectin expression followed treatment with losartan, indicating an Ang II type 1 receptor-mediated effect. Normalization of blood pressure during Ang II infusion by either hydralazine or prazosin had different effects on the level of fibronectin steady-state mRNA, indicating that blood pressure elevation was not the principal factor responsible for fibronectin induction. Concurrent administration of angiotensin-converting enzyme inhibitors with Ang II attenuated the increased fibronectin expression. Our data indicate that Ang II induces an acute fibrotic response within the heart and suggests that Ang II stimulates fibronectin expression within nonmyocytic cardiac cells by a direct action.

Seventh report of the joint national committee on the prevention, detection, evaluation, and treatment of high blood pressure (JNC 7): Resetting the hypertension sails

The National High Blood Pressure Education Program (NHBPEP), coordinated by the National Heart, Lung, and Blood Institute (NHLBI), has released its long-awaited Joint National Committee (JNC) 7 report.1 The report will be made available in 2 forms: the “Express” or short version and a longer version that will be published in Hypertension and will provide more detail regarding the recommendations. On its surface, it resembles the 6 predecessors, but to fully appreciate this new landmark document, one must recognize the process and context from which it is derived and what it is about to do. You cannot direct the winds; you can adjust the sails. Approximately 35 years ago, clinicians were busy managing severe and malignant hypertension. Hospitals filled their beds with stroke patients and stroke wards were commonplace. Coronary heart disease and stroke prevalence and accompanying mortality rates were the highest ever recorded. During the next generation, different classes of antihypertensive agents were developed and tested in a variety of settings and among different patients. The studies independently and collectively contributed to a universal finding: lowering arterial pressure can remarkably reduce cardiovascular morbidity and mortality rates as well as slow the progression of renal disease, retinopathy, and all-cause deaths. When these findings first became available, the NHLBI formed the NHBPEP, designed to translate this information through public and professional education programs. One important step …

Mineralocorticoid-Induced Hypertension in Patients with Orthostatic Hypotension

The mechanism of recumbent hypertension induced by fludrocortisone was studied in seven patients with orthostatic hypotension. All showed increases in blood pressure in the recumbent and standing positions, and hypertensive levels were achieved on recumbency in four of them. Hypertensive retinopathy developed in two patients and cardiomegaly in one. Initial blood-pressure elevations were associated with sodium retention and plasma-volume expansion. However, with long-term treatment, plasma volume decreased to control levels despite further blood-pressure increases. Treatment did not affect plasma levels of catecholamines but did enhance pressor responsiveness to infused norepinephrine in some subjects. Hemodynamic studies indicated that hypertension in the recumbent position was related to increases in total peripheral-vascular resistance and not to changes in cardiac output. Clinically, hypertension in the recumbent position is an important risk of fludrocortisone treatment in patients with orthostatic hypotension. This unusual model of chronic mineralocorticoid-induced hypertension is not volume dependent but is related to increased peripheral-vascular resistance.

Growth Factor Expression in Aorta of Normotensive and Hypertensive Rats

Hypertension causes biochemical and morphological changes in the vessel wall by unknown mechanisms. Locally produced substances may have a role in mediating these vascular changes. We have studied the expression of platelet-derived growth factor (PDGF) B chain and PDGF A chain, insulin-like growth factor (IGF)-I and IGF-II, endothelial cell growth factor (ECGF), basic fibroblast growth factor (bFGF), and transforming growth factor-beta (TGF-beta) in aortic tissue from normotensive rats and rats made hypertensive by deoxycorticosterone (DOC)/salt treatment. Using Northern blotting, we found that genes for each of these growth factors were transcriptionally active in the aorta of both normotensive and hypertensive rats. TGF-beta aortic mRNA levels increased up to threefold as a result of DOC/salt hypertension. In contrast, no major changes in the expression of either PDGF chain, IGF-I or II, ECGF, or bFGF were detectable. The results indicate that at least seven genes coding for growth factors that were shown previously to influence growth and function of vascular cells in vitro, are expressed in rat aorta in vivo. These findings support the hypothesis that synthesis and release of growth factors in the arterial wall are involved in autocrine and/or paracrine regulatory mechanisms. In addition, the increased expression of TGF-beta in vivo may have a role in mediating the aortic changes induced by hypertension.

High-normal blood pressure progression to hypertension in the Framingham Heart Study.

This study sought to determine if individuals with high-normal blood pressure (diastolic blood pressure of 85-89 mm Hg) progress to hypertension more frequently than those with normal blood pressure (diastolic blood pressure less than 85 mm Hg), thus advancing to a higher cardiovascular risk category. Individuals from the Framingham Heart Study were placed in normal and high-normal blood pressure categories and followed for 26 years for the development of hypertension. With hypertension defined as a diastolic blood pressure of 95 mm Hg or greater or the initiation of antihypertensive therapy, 23.6% of men and 36.2% of women with normal blood pressure developed hypertension compared with 54.2% of men and 60.6% of women with high-normal blood pressure. The relative risk for the development of hypertension associated with high-normal blood pressure was 2.25 for men (95% confidence interval [CI], 1.8-2.8; p less than 0.0001) and 1.89 for women (95% CI, 1.5-2.3; p less than 0.0001). The age-adjusted relative risks estimated by the proportional hazards model were 3.36 for men and 3.37 for women (p less than 0.001). Among those risk factors examined, baseline systolic and diastolic blood pressure, Metropolitan relative weight, and change in weight over time were significant predictors of future hypertension in men and women whose initial blood pressure was normal. For men with high-normal blood pressure, systolic blood pressure and change in weight were identified as risk factors for future hypertension. These results indicate that the probability of individuals with blood pressure in the high-normal range developing hypertension is twofold to threefold higher than in those with normal blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal Revascularization in the Azotemic Hypertensive Patient Resistant to Therapy

We undertook this study to assess the frequency of renovascular hypertension in patients with azotemia and hypertension refractory to drug therapy and to determine the effects of renal revascularization on blood pressure and renal function in these subjects. Thirty-nine of 106 consecutive patients admitted for diagnostic evaluation of severe hypertension proved to have renovascular hypertension. Of 21 hypertensive patients with renal insufficiency, 10 appeared to have renovascular hypertension with either bilateral atherosclerotic renovascular disease or unilateral renal arterial stenosis in a solitary functioning kidney. Medical therapy in the hospital often induced further deterioration of renal function despite enhanced blood-pressure control. However, surgical revascularization or percutaneous transluminal angioplasty produced improvement or stabilization of renal function and control of blood pressure in all patients with azotemia who were treated in this manner, despite longstanding hypertension. The benefits of therapy have persisted for 10 to 42 months of follow-up. These studies indicate that refractory hypertension in association with renal insufficiency is a relatively common clinical presentation for renovascular hypertension and bilateral renal-artery disease. Diagnostic evaluation and consideration of renal revascularization appear warranted in such patients, both for the control of the hypertension and for improvement in renal function.