Effect of nitric oxide and potassium channel agonists and
inhibitors on basilar artery diameter.
Sobey, Christopher G., and Frank M. Faraci.
Departments of Internal Medicine and Pharmacology, and
Cardiovascular Center, University of Iowa College of Medicine, Iowa
City, Iowa 52242
APStracts 3:0315H, 1996.
The first goal of this study was to examine the hypothesis that
dilatation of the basilar artery in response to activation of ATP
-sensitive K+ channels is mediated by nitric oxide (NO). Diameter of
the basilar artery (209 5 m, mean SE) was measured using a cranial
window in anesthetized rats. Aprikalim (a direct activator of ATP
-sensitive K+ channels) dilated the basilar artery under control
conditions. Inhibition of endogenous NO production with NG-nitro-L
-arginine (L-NNA, 10-4 M) did not alter responses to aprikalim. The
second goal was to determine whether vasodilatation in response to NO
is dependent on activation of calcium-activated K+ channels.
Tetraethylammonium (TEA, 10-3 M), an inhibitor of calcium-activated
K+ channels, did not affect dilator responses to sodium nitroprusside
(an NO donor) under control conditions. Responses to nitroprusside
(10-8 M and 10-7 M) were augmented more than 2-fold during
application of L-NNA. In the presence of L-NNA, the augmented portion
of the response to nitroprusside was inhibited by TEA and iberiotoxin
(5 x 10-8 M, a highly selective inhibitor of calcium-activated K+
channels), but was not inhibited by glibenclamide (10-6 M), an
inhibitor of ATP-sensitive K+ channels. These findings suggest that
dilator responses of the basilar artery to an activator of ATP
-sensitive potassium channels are not mediated by NO. Calcium
-activated K+ channels may not normally contribute to dilator
responses of the basilar artery to nitroprusside. The effects of TEA
and iberiotoxin suggest that when endogenous production of NO is
inhibited, sodium nitroprusside causes opening of calcium-activated
K+ channels, contributing to an augmented vasodilator response.
Received 2 February 1996; accepted in final form 12 July 1996.
APS Manuscript Number H104-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 August 1996