The vascular effects of topical and intravenous alpha2-adrenoceptor agonist clonidine on canine pial microcirculation.

Abstract

To assess the direct cerebrovascular effects of clonidine, we investigated the pharmacological responses of pial vessels to its topical and i.v. administration using a cranial window. Forty-six dogs anesthetized with pentobarbital had the cranial window implanted. We administered six different concentrations of clonidine (10(-8), 10(-7), 10(-6), 10(-5), 10(-4), 10(-3) mol/L) dissolved in artificial cerebrospinal fluid under the window and measured the pial arterial and venous diameters. After pretreating pial vessels with either yohimbine, an alpha2-adrenoceptor antagonist, or glibenclamide, an adenosine triphosphate-sensitive K+-channel blocker, their action was examined after applying clonidine. We also evaluated the effects of i.v. clonidine (5 microg/kg) on pial vascular tone. Topical clonidine produced significant constriction of the pial large and small arteries and veins in a concentration-dependent manner (P < 0.05). Yohimbine abolished the clonidine-induced pial arterial (large P < 0.005; small P < 0.0005) and venous constriction (large and small P < 0.0001). Glibenclamide potentiated the clonidine-induced pial arterial constriction (P < 0.05). I.v. clonidine did not cause significant changes in pial arteries, but it caused significant constriction of small veins. These were associated with a significant decrease in heart rate and an increase in serum potassium level and glucose concentration. In the present study, we demonstrate that the topical application of clonidine constricts both pial arterial and venous vessels in a concentration-dependent manner and suggest that mechanisms of such action are caused by the activation of alpha2-adrenoceptors and adenosine triphosphate-sensitive K+-channels, whereas i.v. clonidine constricts only pial small veins. In this study, we describe the direct and i.v. effects of clonidine on pial vessels using a cranial window in anesthetized dogs. The topical application of clonidine constricts pial vessels. This is mediated by the activation of alpha2-adrenoceptors and adenosine triphosphate-sensitive K+-channels. I.v. clonidine constricts only pial small veins.