The role of atp-sensitive k+ channels in cgmp-mediated pial artery
vasodilation.
Armstead, W. M.
Departments of Anesthesia and Pharmacology, The University of
Pennsylvania and The Children's Hospital of Philadelphia,
Philadelphia, PA 19104-4399
APStracts 2:0294H, 1995.
The present study was designed to investigate the role of ATP
sensitive K+ channels in cGMP-mediated pial artery vasodilation in
newborn pigs equipped with a closed cranial window. SNP (10-8,10-6M),
a nitrovasodilator, elicited pial artery dilation that was attenuated
by the ATP sensitive K+ channel antagonist, glibenclamide (10-6M). On
a percentage basis, these responses were 25+1% for the presence of
SNP (10-6M) alone, while 15+1% dilation was observed for SNP (10-6M)
in the presence of glibenclamide, n=5. Dilation produced by the cGMP
analogue, 8-[beta]romo-cGMP (10-8,10-6M), was similarly attenuated by
glibenclamide. SNP-induced pial dilation was accompanied by increased
cortical periarachnoid CSF cGMP levels and these biochemical changes
were blocked by the soluble guanylate cyclase inhibitor, LY83583 (10
-5M). SNP (10-6M) alone increased CSF cGMP concentration from 407+14
to 956+41 fmol/ml while SNP in the presence of LY83583 yielded a CSF
cGMP concentration of 340+13, which was no different from the control
value of 335+23 fmol/ml, n=5. SNP-induced pial dilation was blunted
by LY83583 whereas 8-bromo-cGMP-induced dilation was unchanged.
Cromakalim (10-8,10-6M), a ATP sensitive K+ channel agonist, produced
dilation that was blocked by glibenclamide (24+ 1 vs 5+1% for
cromakalim 10-6M, in the absence and presence of glibenclamide,
respectively, n=5). These data indicate that activation of ATP
sensitive K+ channels contribute to cGMP-mediated pial artery
dilation.
Received 17 March 1995; accepted in final form 27 June 1995.
APS Manuscript Number H262-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 18 July 1995.