© 1995 American Heart Association, Inc.
Articles |
Dilatation of Cerebral Arterioles in Response to Activation of Adenylate Cyclase Is Dependent on Activation of Ca2+-Dependent K+ Channels
From the Departments of Internal Medicine and Pharmacology, Cardiovascular Center and Center on Aging, University of Iowa College of Medicine, Iowa City.
Correspondence to Frank M. Faraci, PhD, Department of Internal Medicine, Cardiovascular Center, University of Iowa College of Medicine, Iowa City, IA 52242.
Abstract The role of Ca2+-dependent potassium channels in mediating vascular responses to activation of adenylate cyclase in vivo is not known. The goal of this study was to examine the hypothesis that dilatation of cerebral arterioles in response to activation of adenylate cyclase is mediated by activation of Ca2+-dependent potassium channels. Diameters of cerebral arterioles were measured in vivo in anesthetized rabbits. Topical application of forskolin (1 and 10 µmol/L), a direct activator of adenylate cyclase, dilated cerebral arterioles by 40±8% (mean±SEM) and 71±9%, respectively, from a control diameter of 85±4 µm. Iberiotoxin (50 and 100 nmol/L), a selective inhibitor of Ca2+-dependent potassium channels, inhibited dilatation in response to both concentrations of forskolin by 45% to 60%. We obtained similar results by using charybdotoxin (50 nmol/L), another inhibitor of Ca2+-dependent potassium channels. Vasodilatation in response to dibutyryl cAMP (a cell-permeable cAMP analogue) was also inhibited by iberiotoxin. In contrast, dilatation of cerebral arterioles in response to sodium nitroprusside and acetylcholine (activators of guanylate cyclase) and aprikalim (activator of ATP-sensitive potassium channels) was not inhibited by iberiotoxin. These findings suggest that dilatation of cerebral arterioles in response to forskolin and increases in intracellular concentrations of cAMP are mediated by activation of Ca2+-dependent potassium channels. Thus, activation of Ca2+-dependent potassium channels may be a major mechanism of cerebral vasodilatation in response to activation of adenylate cyclase in vivo.
Key Words: cerebral arterioles • forskolin • sodium nitroprusside • aprikalim • iberiotoxin
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