Ronald Victor, M.D.
Professor of Medicine
Chief, Division of Hypertension

Wanpen Vongpatansin, M.D.
Assistant Professor of Medicine
Division of Hypertension

1. Mechanism and Treatment of High Normal Blood Pressure. Grant: Donald W. Reynolds Foundation-PI: Victor. People with high-normal blood pressures are at increased risk for progression to full blown hypertension and for heart disease and stroke. However, physicians currently do not treat individuals with such borderline blood pressure elevations. The goal of this study is to determine if there are gain-of-function mutations either in the mineralocorticoid receptor or the epithelial sodium channel that contribute to high-normal blood pressure and that constitute effectrive drug targets to turn high normal into optimal blood pressures, thereby reducing cardiovascular risk. Black and white men and women with high normal blood pressures will be randomized to 8 weeks of treatment with a low dose of either spironolactone, which blocks the mineralocorticoid receptor, amiloride which blocks the epithelial sodium channel, both, or placebo. Blood pressures will be measured with ambulatory monitoring and plasma and urine electrolytes and hormones will be carefully monitored with patients on a metabolic diet. Whole genome scans will be performed on DNA from the subjects who show the greatest and the least responses to the different treatments.

2. The Metabolic Syndrome in Blacks. Grant: Donald W. Reynolds Foundation-PI:Victor. Compared with whites, blacks have more clustering of cardiovascular risk factors including hypertension, obesity, and insulin resistance. Our recent work implicates an important role for the sympathetic nervous system in linking obesity with hypertension in blacks, as well as whites, but we do not yet know how increasing fat mass signals the sympathetic nervous system to increase its activity. Our working hypothesis is two-fold: (1) that increase sympathetic nerve activity in skeletal muscle is a marker of the metabolic syndrome, and (2) that hormonal substances produced by adipocytes circulate to the brain and activate the sympathetic nervous system. To test these hypotheses, we will measure body fat with DEXA scans and abdominal MIRI, record sympathetic nerve activity (microelectrodes), and measure plasma levels of adiponectin and resistin (2 newly discovered hormones produced by adipocytes) in healthy young adult black men and women with and without a family history of hypertension. We predict that, for the same BMIs, subjects with high levels of sympathetic activity will have more adverse metabolic profiles (higher insulins, higher triglycerides, lower HDL cholesterols) along with lower blood levels of adiponectin, which is thought to be cardioprotective, and higher levels of resistin, which is thought to engender insulin resistance.

3. Oxidative Stress and Muscle Blood Flow. Grant: NIH Program Project Grant-PI: Victor, Thomas. Our recent work in rats indicates that blood flow to exercising muscles is finely regulated by the balance between production of nitric oxide and its inactivation by reactive oxygen species. Both are produced by the contracting muscle fibers. The goal of this study is to determine the extent to which we can translate this basic research to humans. We will use two different strategies to increase the production of reactive oxygen species in healthy subjects: (1) nitrate tolerance caused by wearing a nitroglycerine patch for several days, or (2) continuous intravenous infusion of angiotensin II. We will measure oxygen delivery to resting and exercising forearm muscles using near infrared spectroscopy.

4. Estrogen Hormone Replacement and Muscle Blood Flow. Grant: NIH RO1-PI:Thomas. Our recent studies in rats indicates that the normal production of nitric oxide by skeletal muscle is dependent upon estrogens. Ovariectomy produces nitric oxide deficiency and impairs blood flow to exercising skeletal muscle. To determine if we can extend these results to postmenopausal women, we are measuring oxygenation of exercising forearm muscles (near infrared spectroscopy) in healthy postmenopausal women randomized to estrogen replacement or placebo.

5. Estrogen Hormone Replacement and Blood Pressure. Grant: NIH K23-PI:Vongpatanasin. Before menopause, women are generally protected from hypertension and heart disease. After menopause, the incidence of hypertension and heart disease rises dramatically. However, clinical trials with oral estrogen replacement therapy have produced disappointing results both on hypertension and heart disease. The goal of this study is to test the hypothesis that the route of adminstration of estrogens has a big impact on its cardioprotective effects. Postmenopausal women with mild or moderate hypertension will be randomized to treatment with either oral or transdermal estrogen or placebo. We predict that only transdermal estrogen will lower blood pressure and improve the metabolic risk profile because this route of administration avoids first-pass hepatic metabolism, which activates inflammatory cytokines.

6. Cardiovascular Consequences of Chronic Cocaine Abuse. Grant: NIH RO1-PI: Victor, Vongpatansin. Although cocaine abuse has increased to epidemic proportions and is known to cause acute cardiovascular emergencies (e.g., hypertensive crisis, heart attack), the long-term cardiovascular sequelae are poorly understood. The aim of this study is to test the hypothesis that the repeated increases in sympathetic activity and blood pressure that accompany chronic cocaine abuse cause hypertrophy and decreased distensibility of the aorta. We further hypothesize that this structural damage impairs the ability of the baroreceptors to defend against sudden increases in blood pressure during common daily stresses such as with mild exercise of cigarette smoking. To test these hypotheses, we will measure aortic wall thickness and elasticity with magnetic resonance imaging and sympathetic nerve activity with microelectrodes in chronic cocaine abusers recruited from the rehabilitation unit at the Veterans Administration Hospital.

7. Controlling Hypertension in Black Men. Grant: Texas Higher Education Board-PI:Victor,Freeman. Black men are the demographic group in the U.S. with the greatest rates of hypertension but the lowest rates of hypertension awareness, treatment, and control. This public health study will test the hypothesis that barbershops are effective places to detect black men with untreated hypertension and institute educational programs to enhance the awareness, treatment, and control of hypertension in this high-risk group. To test this hypothesis, we will screen blood pressures in barbershops to recruit several hundred black men with uncontrolled hypertension and then randomize shops to control vs. intervention, the latter employing state-of-the-art behavioral strategies to increase the participants' participation in their own health care/blood pressure control. Incentives will include discounted haircuts. The outcome measure will be blood pressures measured in the barbershops.