© 1996 American Heart Association, Inc.
Articles |
Acidosis-Induced Coronary Arteriolar Dilation Is Mediated by ATP-Sensitive Potassium Channels in Vascular Smooth Muscle
From the Department of Medical Physiology, Microcirculation Research Institute, Texas A&M University Health Science Center, College Station, Tex.
Correspondence to Lih Kuo, PhD, Department of Medical Physiology, Microcirculation Research Institute, Texas A&M University Health Science Center, College Station, TX 77843-1114. E-mail lkuo@tamu.edu.
Abstract Although a decrease in extravascular pH has been
suggested to be involved in coronary flow regulation during
hypoxia, ischemia, and increased metabolic
demand of the heart, its vasomotor control mechanism has not been
elucidated. To examine the effect of acidosis on vasomotor tone,
porcine coronary arterioles (40 to 110 µm) were isolated,
cannulated, and pressurized to 60 cm H2O intraluminal
pressure without flow for in vitro study. Acidosis (pH 7.4 to 7.0) was
produced by adding HCl to the extravascular solution. The involvement
of potassium channels in the vasomotor response to acidosis was
evaluated by using BaCl2 (100 µmol/L, nonspecific
potassium channel inhibitor), glibenclamide (5 µmol/L,
ATP-sensitive potassium channel inhibitor), and iberiotoxin
(100 nmol/L, calcium-activated potassium channel
inhibitor). To determine whether
endothelial hyperpolarization
contributes to the acidosis-induced dilation, the pH-diameter
relation of the vessel was examined under a high intraluminal
concentration of KCl (40 mmol/L). The involvement of nitric oxide and
prostaglandins was assessed by using
NG-monomethyl-L-arginine
(L-NMMA, 10 µmol/L) and indomethacin (10 µmol/L),
respectively. To evaluate the role of endothelium in
the acidosis-induced dilation, the pH-diameter relation was studied
after endothelial removal. All vessels developed a
similar level of spontaneous tone (internal diameter, 75±4 µm
[
69±1% of maximum diameter]) and dilated to HCl in a
dose-dependent manner. Glibenclamide completely abolished
vasodilation to a mild level of acidosis (pH 7.2 to 7.3) and attenuated
the vasodilation by 70% at pH 7.0. Acidosis-induced dilation was
also inhibited by BaCl2 but not by iberiotoxin. L-NMMA,
indomethacin, and intraluminal KCl did not alter the
pH-diameter relation. Vasodilation to acidosis of the
endothelium-denuded vessels was identical to that
of the endothelium-intact vessels. In addition,
glibenclamide attenuated the acidosis-induced arteriolar dilation
of endothelium-denuded vessels in a manner similar
to that of endothelium-intact vessels. These
results suggest that the opening of ATP-sensitive potassium channels in
vascular smooth muscle mediates the coronary arteriolar
dilation during acidosis.
Key Words: endothelium • microcirculation • nitric oxide • prostaglandins • vasodilation
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