(Stroke. 1996;27:1603-1608.)
© 1996 American Heart Association, Inc.
Articles |
Role of Ca2+-Dependent K+ Channels in Cerebral Vasodilatation Induced by Increases in Cyclic GMP and Cyclic AMP in the Rat
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, University of Iowa College of Medicine, Iowa City, IA 52242-1081.
Background and Purpose The mechanisms by which cAMP and cGMP produce vasorelaxation are not entirely clear. In this study we examined the hypothesis that relaxation of cerebral arterioles in response to receptor-mediated activation of adenylate cyclase (increase in cAMP) is mediated through Ca2+-dependent K+ channels.
Methods We measured the diameter of cerebral arterioles (basal diameter, 47±1 µm) using an open cranial window in anesthetized rats. Agonists and antagonists were applied locally in the cranial window.
Results Topical application of adenosine (0.1 and 1 mmol/L), a receptor-mediated activator of adenylate cyclase, and dibutyryl cAMP (60 and 200 µmol/L), a cell-permeable analogue of cAMP, dilated cerebral arterioles. Iberiotoxin (50 nmol/L), a selective inhibitor of Ca2+-dependent K+ channels, reduced vasodilatation in response to 0.1 and 1 mmol/L adenosine by 66% and 28%, respectively. Tetraethylammonium (TEA) (1 mmol/L), another inhibitor of Ca2+-dependent K+ channels, reduced vasodilatation to 0.1 and 1 mmol/L adenosine by 58% and 42%, respectively, and reduced vasodilatation in response to 60 and 200 µmol/L dibutyryl cAMP by 75% and 66%, respectively. Topical application of sodium nitroprusside (0.1 and 1 µmol/L), a direct activator of guanylate cyclase, and 8-bromo cGMP (200 and 600 µmol/L), a cell-permeable analogue, produced dilatation of cerebral arterioles that was inhibited by iberiotoxin (50 nmol/L) and TEA (1 and 3 mmol/L). In contrast, dilatation of cerebral arterioles in response to papaverine (which produces vasodilatation in large part by inhibition of Ca2+ channels) and aprikalim (which produces vasodilatation by activation of ATP-sensitive K+ channels) was not inhibited by iberiotoxin or TEA.
Conclusions These findings suggest that dilatation of cerebral arterioles by receptor-mediated activation of adenylate cyclase and by direct activation of guanylate cyclase in the rat is mediated in large part by activation of Ca2+-dependent K+ channels.
Editorial Comment
Department of PharmacologySmooth Muscle Ion Channel GroupUniversity of Vermont Medical Research FacilityColchester, Vt
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