(Stroke. 1997;28:2290-2295.)
© 1997 American Heart Association, Inc.
Articles |
Mechanisms of Bradykinin-Induced Cerebral Vasodilatation in Rats
Evidence That Reactive Oxygen Species Activate K+ Channels
From the Departments of Internal Medicine (C.G.S., D.D.H., F.M.F.) and Pharmacology (D.D.H., F.M.F.), Cardiovascular Center, University of Iowa College of Medicine, Iowa City.
Correspondence to Frank M. Faraci, PhD, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA 52242.
Background and Purpose Relatively little is know regarding mechanisms by which reactive oxygen species produce dilatation of cerebral arterioles. The goal of this study was to test the hypothesis that vasodilator responses of cerebral arterioles to bradykinin, which produces endogenous generation of reactive oxygen species, involve activation of calcium-dependent potassium channels.
Methods We used a cranial window in anesthetized rats to examine effects of catalase (which degrades hydrogen peroxide) on responses to bradykinin. In addition, we examined effects of tetraethylammonium (TEA) and iberiotoxin, inhibitors of calcium-dependent potassium channels, on responses of cerebral arterioles to hydrogen peroxide, bradykinin, and papaverine.
Results In cerebral arterioles (baseline diameter=40±1 µm) (mean±SE), hydrogen peroxide (10 and 100 µmol/L) produced concentration-dependent dilatation. TEA (1 mmol/L), an inhibitor of calcium-dependent potassium channels, produced marked inhibition of vasodilatation in response to hydrogen peroxide. For example, 100 µmol/L hydrogen peroxide dilated arterioles by 13±2% in the absence and 4±1% (P<.05 versus control) in the presence of TEA. Bradykinin (10 nmol/L to 1 µmol/L) also produced concentration-dependent dilatation of cerebral arterioles that was inhibited completely by catalase (100 U/mL). TEA or iberiotoxin markedly inhibited vasodilatation in response to bradykinin. For example, 100 nmol/L bradykinin dilated arterioles by 21±3% in the absence and 2±2% (P<.05 vs control) in the presence of iberiotoxin (50 nmol/L).
Conclusions These findings suggest that dilatation of cerebral arterioles in the rat in response to hydrogen peroxide, or hydrogen peroxide produced endogenously in response to bradykinin, is mediated by activation of calcium-dependent potassium channels. Thus, activation of potassium channels may be a major mechanism of dilatation in response to reactive oxygen species in the cerebral microcirculation.
Key Words: bradykinin • cerebral arteries • vasodilation • rats
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