Role of activation of calcium-sensitive k+ channels in nitric oxide
and hypoxia-induced pial artery vasodilation.
Armstead, W. M.
Departments of Anesthesia and Pharmacology, University of
Pennsylvania and The Children's Hospital of Philadelphia,
Philadelphia, PA
APStracts 3:0525H, 1996.
It has been previously observed that nitric oxide (NO) contributes to
hypoxic pial artery dilation and that both sodium nitroprusside
(SNP), a releaser of NO, and hypoxia elicit dilation via activation
of ATP-sensitive K+ channels in the newborn pig. Other studies,
however, have shown that NO activates calcium sensitive K+ (Kca+2)
channels . The present study, therefore, was designed to investigate
the role of Kca+2 channel activation in NO and hypoxic dilation and
to relate this mechanism to the previously observed role of NO in
hypoxic dilation in newborn pigs equipped with closed cranial
windows. SNP (10-8,10-6 M) elicited pial artery dilation that was
unchanged in the presence of the Kca+2 channel antagonist,
iberiotoxin (10-7 M) (10+/-1 and 20+1 vs 9+1 and 20+2% for SNP 10-8,
10-6M in the absence and presence of iberiotoxin, respectively).
Responses to SNAP and 8-Bromo cGMP were similarly unchanged by
iberiotoxin. In contrast, iberiotoxin attenuated the dilation
resulting from moderate and severe hypoxia (arterial Po2 nearly equal
to 35 and 25mmHg, respectively) (27+1 vs 21+2 and 34+1 vs 16+2% for
moderate and severe hypoxia in the absence and presence of
iberiotoxin, respectively). Iberiotoxin blocked responses to the
Kca+2 channel agonist NS 1619 while responses to the ATP-sensitive K+
agonist, cromakalim, were unchanged (8+1 and 15+1 vs 1+1 and 1+1% for
NS 1619 10-8, 10-6M in the absence and presence of iberiotoxin,
respectively). These data show that NO and cGMP do not elicit
dilation via Kca+2 channel activation. However, activation of Kca+2
channels does contribute to hypoxic pial dilation. Finally, these
data suggest that substances other than NO are involved in the
contribution of Kca+2 channel activation to hypoxic pial artery
dilation.
Received 8 July 1996; accepted in final form 14 November 1996.
APS Manuscript Number H598-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996