Arginine analogues inhibit responses mediated by atp-sensitive k+
channels.
Kontos, Hermes A., and Enoch P. Wei.
Dept. of Medicine, Medical College of VA, VA Commonwealth
University, Richmond, VA 29298
APStracts 3:0174H, 1996.
Since arginine analogues have been reported to block the vasodilator
response to hypercapnia, we investigated the effect of nitro-L
-arginine (L-NNA) on the dilation of pial arterioles to arterial
hypercapnia induced by inhalation of 3, 5, and 7% CO2 in anesthetized
cats equipped with cranial windows. L-NNA at 250 [mu]M, but not at
lower concentrations, significantly reduced hypercapnia-induced
dilation. This effect could be reversed by L-arginine. However,
hypercapnic hyperemia is not the result of increased cGMP via the
usual NO-mediated activation of guanylate cyclase, because
application of LY83583 which blocks guanylate cyclase did not alter
the vessel response to CO2. L-NNA at 250 [mu]M also abolished the
pial arteriolar dilation in response to cromakalim, minoxidil and
pinacidil, three known openers of ATP-sensitive K+ channels, and this
effect could be reversed by L-arginine. Application of glyburide,
which blocks ATP-sensitive K+ channels, also reduced the response to
CO2. Subsequent application of L-NNA in these experiments had no
additional effect. Vasodilation induced by sodium nitroprusside and
SIN-1, two known NO donors, was unaffected by glyburide. NG
-monomethyl-L-arginine (L-NMMA) was found to have effects similar to
those of L-NNA in both cat and rat in doses as low as 20 [mu]M. Our
findings suggest that arginine analogues inhibit hypercapnic
vasodilation by blocking ATP-sensitive K+ channels, independently of
activation of guanylate cyclase via increased production of NO.
Furthermore, the data suggest that ATP-sensitive K+ channels may have
an arginine site which influences their function.
Received 8 November 1995; accepted in final form 8 April 1996.
APS Manuscript Number H1047-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 May 96