Enhanced role of potassium channels in relaxations of
hypercholesterolemic rabbit carotid artery to nitric oxide and sodium
nitroprusside.
Cohen, Soheil Najibi Richard A.
Vascular Biology Unit, Robert Dawson Evan's Department of Clinical
Research, Boston University Medical Center, Boston, MA
APStracts 2:0082H, 1995.
Endothelium-dependent relaxations to acetylcholine remain normal in
the carotid artery of hypercholesterolemic rabbits, but unlike
endothelium-dependent relaxations of normal rabbits, they are
inhibited by charybdotoxin, a specific blocker of calcium-dependent
potassium channels (K+Ca). Because nitric oxide (NO) is the mediator
of endothelium-dependent relaxation and can activate K+Ca directly or
via cGMP, the present study investigated the role of K+Ca in
relaxations caused by nitric oxide (NO), sodium nitroprusside, and 8
-bromo-cGMP in hypercholesterolemic rabbit carotid artery. Isometric
tension was measured in rabbit carotid artery denuded of endothelium
from normal and hypercholesterolemic rabbits which were fed 0.5%
cholesterol for 12 weeks. Under control conditions, relaxations to
all agents were similar in normal and hypercholesterolemic rabbit
arteries. Charybdotoxin had no significant effect on relaxations of
normal arteries to nitric oxide, sodium nitroprusside, or 8-bromo
-cGMP, but the K+Ca blocker significantly inhibited the relaxations
caused by each of these agents in the arteries from
hypercholesterolemic rabbits. By contrast, relaxations to the calcium
channel blocker, nifedipine, were potentiated to a similar extent by
CTX in both groups. In addition, arteries from hypercholesterolemic
rabbits relaxed less than normal to sodium nitroprusside when
contracted with depolarizing potassium solution. These results
indicate that although nitrovasodilator relaxations are normal in the
hypercholesterolemic rabbit carotid artery, they are mediated
differently, and to a greater extent by K+Ca. These data also suggest
that potassium channel-independent mechanism(s) are impaired in
hypercholesterolemia.
Received 8 December 1994; accepted in final form 1 March 1995.
APS Manuscript Number H1075-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 21 March 1995.