DUAL EFFECT OF CLONIDINE ON MESENTERIC-ARTERY ADRENOCEPTORS - AGONISTIC (ALPHA-2) AND ANTAGONISTIC (ALPHA-1)

The effect of clonidine on the mesenteric vascular bed and the isolate d mesenteric artery was examined in preparations in which tonus was in duced by norepinephrine or endothelin. In preparations precontracted b y norepinephrine, clonidine caused a relaxation which was not inhibite d by the alpha-2 antagonists yohimbine and idazoxan or by the K+ chann el blockers apamine, tetraethylammonium and glibenclamide. In preparat ions precontracted with endothelin, clonidine increased the depolariza tion and induced a contraction. Both these effects were inhibited by p razosin. In isolated mesenteric arteries, norepinephrine caused a sign ificant depolarization that was inhibited by clonidine or prazosin. On the other hand, clonidine caused a hyperpolarization which was inhibi ted by idazoxan or yohimbine, but not by prazosin. This hyperpolarizat ion was also abolished by apamine, tetraethylammonium and glibenclamid e. It is concluded that clonidine acts on alpha-1 adrenoceptors as a p artial agonist, causing relaxation of the mesenteric artery precontrac ted with norepinephrine or contraction of preparations precontracted w ith endothelin. Moreover, clonidine can open K+ channels and hyperpola rize the plasma membrane of mesenteric artery by acting on alpha-2 adr enoceptors.