Functional distribution and role of alpha-1 adrenoceptor subtypes in the mesenteric vasculature of the rat.
Because alpha-1 adrenoceptor subtypes are distributed differentially in different arteries, experiments were conducted to determine the functional contribution of these subtypes in conduit vs. resistance vessels. Concentration- or dose-response curves for norepinephrine were obtained from aortic rings, superior mesenteric artery rings or the isolated perfused mesenteric vasculature from male Sprague-Dawley rats. Frequency-response curves to transmural electrical stimulation were obtained from the latter two preparations. The effects of 5-methylurapidil (5-MU), an alpha-1a adrenoceptor antagonist, and chloroethyl-clonidine (CEC), an alpha-1b adrenoceptor antagonist, on contractile responses were determined. In artery rings, 5-MU (30 nM) had no effect on the EC50 of norepinephrine but reduced the maximum response of the mesenteric artery rings by nearly 25%. In the perfused mesenteric vasculature, however, 5-MU (30 nM) shifted the ED50 for norepinephrine about 40-fold while reducing the maximum response by 30%. 5-MU depressed the frequency-response curve in the perfused mesenteric vasculature by nearly 80%, but did not alter the response of artery rings. In aorta, pretreatment with CEC (10 microM) shifted the concentration-response curve of norepinephrine by 800-fold without effecting the maximum. In mesenteric artery rings and perfused mesenteric vasculature, CEC reduced the slope and maximum response of both frequency-response and norepinephrine dose-response curves. Responses to norepinephrine (10 microM) in the perfused mesentery were abolished by 5-MU and reduced only 25% by nifedipine. These data suggest that the density or role of alpha-1a adrenoceptors may be greater in resistance vessels than in conduit vessels.
Kong
J Q
JQ
Department of Pharmacology and Toxicology, West Virginia University Health Sciences Center, Morgantown.
Taylor
D A
DA
Fleming
W W
WW
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism* / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism* / Q000502:physiology
D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; C057446:5-methylurapidil; C051731:chlorethylclonidine; D003000:Clonidine; D002118:Calcium