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Stroke, Vol 20, 238-241, Copyright © 1989 by American Heart Association

ARTICLES

Mechanisms of vascular supersensitivity in hypercholesterolemia

TA McCalden and RG Nath
Department of Pharmacology, University of Houston, Texas.

We have characterized in vitro, for the first time, the phenomenon of acute interaction between hypercholesterolemia and cerebrovascular function. We then used this model to investigate a number of mechanisms for the interaction. Rabbits fed a diet supplemented with 2% cholesterol developed hypercholesterolemia over 4 weeks with no histologically detectable atherosclerosis. This absence of anatomic change was reflected in normal biophysical elastic responses to graded radial stretch and normal optimum tension for responses to exogenous K+ in the selected arteries. However, basilar arteries removed from cholesterol-fed rabbits showed abolished myogenic responses to radial stretch and decreased median effective doses for added norepinephrine. These potentiated constrictor responses to norepinephrine were significantly correlated with increased plasma cholesterol concentration. A mechanism related to the opening of membrane calcium channels may be responsible for the supersensitivity.

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