Date of Award

6-1-1999

Degree Type

Restricted Access Dissertation

Degree Name

Doctor of Philosophy

Field of Study

Biomedical Sciences

Department

Graduate School of Biomedical Sciences

First Advisor

Patricia A. Gwirtz

Second Advisor

Xiangrong Shi

Third Advisor

Peter B. Raven

Abstract

Kline, Geoffrey Philip, Dysfunctional Control of Coronary Blood Flow in Renovascular Hypertension Doctor of Philosophy (Biomedical Sciences), June 1999, 98 pp, 2 tables, 10 figures, references, 142 titles. This study was designed to determine the effects of renovascular hypertension (RVH) on coronary vasoreactivity in conscious, chronically instrumented dogs. Six dogs were instrumented to measure left ventricular pressure, +dP/dtmax, heart rate, mean aortic pressure, circumflex blood flow (CBF), and cardiac output. In order to examine endothelial-dependent and independent coronary vasodilation, intracoronary injections of actylcholine (Ach), bradykinin (BDK), and sodium nitroprusside (SNP) were studied before and after induction of RVH in the presence and absence of nitric oxide (NO) blockade. After RVH, resting CBF was significantly reduced (P<0.05). In the normotensive state, NO-blockade significantly reduced the coronary vasodilation to Ach and BDK (P<0.05), but not SNP. After RVH, the coronary vasodilation to Ach, BDK, and SNP were reduced (P<0.05). After RVH, NO-blockade further reduced the coronary vasodilation to BDK (P<0.05), but not Ach. Thus, RVH resulted in an impairment of both endothelial-dependent and –independent coronary vasodilation. It also appears that during RVH the endothelium retains the ability to produce/release NO to some, but not all, stimuli. In order to examine the possibility that β-adrenergic mediated coronary vasodilation is impaired after RVH, intracoronary injections of norepinephrine (NE), isoproterenol (ISO), and terbutaline (TRB) were administered. These drugs all caused dose dependent increases in CBF before and after RVH. After RVH, the coronary vasodilatory responses to NE, ISO and TRB were significantly reduced (P<0.05). β1-blockade with intracoronary atenolol (1 mg) reduced the ISO-induced increases in CBF and had no effect on TRB responses (P<0.05). β2-blockade with intracoronary ICI-118,551 (1 mg) reduced the ISO-induced coronary vasodilation and abolished TRB responses (p<0.05). During β2-blockade, ISO-induced increases in CBF were not different after RVH. Therefore, these data indicate that β1-adrenergic mediated coronary vasodilation is preserved after RVH, whereas, β2-mediated is not. We conclude that 1) RVH results in an impairment of both endothelial-dependent and –independent coronary vasodilation; 2) RVH results in an impairment of β2-adrenergic mediated coronary vasodilation.

Comments

Kline, Geoffrey Philip, Dysfunctional Control of Coronary Blood Flow in Renovascular Hypertension Doctor of Philosophy (Biomedical Sciences), June 1999, 98 pp, 2 tables, 10 figures, references, 142 titles. W 4 K65D 1999

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