ADRENERGIC LIMITATION OF CORONARY FLOW DURING EXERCISE

  • Gwirtz, Patricia (PI)

Project Details

Description

DESCRIPTION (Adapted from the applicant's abstract): Hypertensive patients
have a limited tolerance to exercise, but the mechanistic reasons for this
limitation are not clear. Studies from the PI's laboratory in chronically
instrumented dogs indicate that during exercise an alpha1 - adrenergic
constrictor tone competes with coexisting metabolic and endothelial mediated
vasodilation in the coronary vasculature. These studies indicate that a
coronary constrictor tone is exaggerated in dogs with renovascular
hypertension. The goal of this proposal is to determine the adrenergic and
neurohumoral mechanisms responsible for the greater coronary vascular
resistance after renovascular hypertension. The general hypothesis to be
tested is that renovascular hypertension alters the neural, paracrine and
autocrine control systems of the coronary circulation through exaggeration
of vasoconstrictor inputs and attenuation of vasodilator influences. These
alterations would cause exaggerated vasoconstrictor reflex influences on the
coronary vessels and a reduced ability to increase coronary blood flow. The
applicant proposes that the renovascular hypertension-induced imbalance
among vasoconstrictor and dilator mechanisms results in a reduction in
myocardial work efficiency and an increased susceptibility to myocardial
hypoperfusion and ischemia, especially during exercise. The long-range goal
is to demonstrate that coronary blood flow regulation is the result of
interactions between neural, hormonal and endothelial control mechanisms.
However, the concept is that under pathophysiological conditions, the
balance between these control mechanisms is altered such that
vasoconstriction dominates. The applicant indicates that the results of
these experiments should address fundamental questions regarding alterations
in sympathetic nervous system and endothelial function and the mechanisms by
which these systems are altered by renovascular hypertension. The applicant
also suggests that these studies should clarify the mechanistic rationale
for different medical therapies to treat patients with hypertension. The
following hypotheses will be tested both in vivo using conscious
instrumented dogs and in vitro using isolated coronary vessel models. 1)
Renovascular hypertension increases coronary vasoconstriction at rest and
during exercise such that the myocardium, specifically the endocardium,
becomes hypoperfused in relation to oxygen demand. 2) Renovascular
hypertension induced changes in coronary vascular function are due to
adaptations in the vascular neural-humoral control mechanisms.
StatusFinished
Effective start/end date31/12/8915/01/98

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