The mechanism for the clonidine-induced coronary artery dilatation in the canine heart.
Clonidine-induced coronary vasodilation was studied in anesthetized dogs pretreated with propranolol to achieve beta-adrenoceptor blockade. The left circumflex coronary artery (LCX) was perfused with arterial blood from a reservoir maintained under a constant pressure of 100 mm Hg. Clonidine when administered directly into the coronary vascular bed in doses of 30, 100, and 300 micrograms induced a dose dependent coronary vasodilation, which was inhibited by cimetidine, but not by idazoxan, methysergide, methylscopolamine, yohimbine, diphenhydramine, ketanserin, or theophylline. A coronary artery vasoconstrictor effect was not observed at higher or lower doses of clonidine. Two other alpha 2-adrenoceptor agonists, UK-14304 and BHT-920, or the mixed alpha-adrenoceptor agonist norepinephrine produced neither consistent vasodilation nor vasoconstriction. Animals made thrombocytopenic by the administration of canine antiplatelet antibodies showed the same vasodilator response to clonidine as animals with normal circulating platelet counts. These observations suggest that clonidine acts directly on the canine coronary H2 receptors and that alpha 2, H1, serotonergic, muscarinic, purinergic, and platelet dependent mechanisms are not involved in the clonidine-induced coronary vasodilation.
Söhngen
W
W
University of Michigan Medical School, Department of Pharmacology, Ann Arbor 48109.
Winbury
M M
MM
Kitzen
J M
JM
Ventura
A
A
Lucchesi
B R
BR
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002927:Cimetidine / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D010477:Perfusion; D011983:Receptors, Purinergic / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology; D014665:Vasodilator Agents
D000316:Adrenergic alpha-Agonists; D000959:Antihypertensive Agents; D011983:Receptors, Purinergic; D014665:Vasodilator Agents; D012701:Serotonin; D002927:Cimetidine; D006632:Histamine; D003000:Clonidine