Antagonism of norepinephrine by clonidine in the isolated rat mesenteric vascular bed.
Experiments were done in isolated, perfused mesenteric vascular beds from Sprague-Dawley rats. Bolus injections of norepinephrine (3-100 nmol) induced dose-dependent increases in perfusion pressure with a maximum increase greater than 100 mm Hg. In the same dose range, clonidine had no effect on perfusion pressure. In the presence of an elevated pressure caused by constant infusions of norepinephrine (6-20 microM), bolus injections of clonidine (0.1-10 nmol) or acetylcholine (0.007-7 nmol) caused dose-related decreases in perfusion pressure. Procedures which damage endothelium (brief exposure to methylene blue or reactive oxygen radicals) abolished the depressor action of acetylcholine but only moderately reduced the depressor action of clonidine. The depressor action of clonidine was not antagonized by the alpha-2 adrenoceptor antagonist, idazoxan. Acetylcholine produced depressor responses in the presence of 5-hydroxy-tryptamine or vasopressin, but clonidine did not. Dose-response curves to bolus doses of norepinephrine were shifted markedly to the right by an alpha-1 selective concentration of prazosin (1 nM) and were shifted to the right with depression of maximum by infusions of clonidine (0.3 and 1.0 microM). It is concluded that, in the mesenteric vasculature of the rat: 1) the role of alpha-2 adrenoceptors, in responses to clonidine, is minimal; 2) endothelial factors play little role, if any, in the depressor effects of clonidine and 3) clonidine has a potent ability to interfere with the alpha-1 adrenoceptor-mediated vasoconstriction induced by norepinephrine. This antagonistic action may be at the level of the receptor but could involve postreceptor steps.
Department of Pharmacology and Toxicology, West Virginia University, Morgantown.
J Q
JQ
Kong
D A
DA
Taylor
W W
WW
Fleming
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology; D009638:Norepinephrine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology; D013152:Splanchnic Circulation / Q000187:drug effects*
D009569:Nitric Oxide; D012701:Serotonin; D003000:Clonidine; D000109:Acetylcholine; D009638:Norepinephrine