Beta adrenoceptor subtype in isolated human, monkey and dog epicardial coronary arteries.
Isolated human, Japanese monkey and dog epicardial coronary arteries and dog renal and mesenteric arteries treated with phentolamine responded to isoproterenol with a concentration-related relaxation. The KB values of metoprolol, a beta-1 antagonist, in the coronary arteries from different mammals did not differ, but were appreciably smaller than those in the dog renal and mesenteric arteries. Treatment with butoxamine, a beta-2 antagonist, inhibited the relaxation of dog mesenteric arteries to a greater extent than that of monkey and dog coronary arteries. Terbutaline, a beta-2 agonist, produced a greater relaxation in monkey mesenteric and dog renal and mesenteric arteries than in human, monkey and dog coronary arteries. Norepinephrine relaxed the monkey and dog coronary arteries dose-dependently via mainly beta-1 adrenoceptors, but elicited a contraction or a minute relaxation in dog mesenteric arteries even when treated with high concentrations of phentolamine. Contractile responses to electrical stimulation of adrenergic nerves in monkey coronary arteries were potentiated by treatment with metoprolol and propranolol, whereas the contractions in dog mesenteric arteries were unaffected. It is concluded that the amine-induced relaxation of human and monkey epicardial coronary arteries is mediated mainly by beta-1 adrenoceptor subtype, as is the response of dog coronary arteries. Involvement of beta-1 subtype in coronary artery relaxations would be a mechanism underlying potentiation by beta antagonists of the contraction caused by norepinephrine released from adrenergic nerves in primates.
Toda
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N
Department of Pharmacology, Shiga University of Medical Sciences, Ohtsu, Japan.
Okamura
T
T
D000818:Animals; D002078:Butoxamine / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D004347:Drug Interactions; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D008251:Macaca; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D008790:Metoprolol / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011817:Rabbits; D011941:Receptors, Adrenergic / Q000187:drug effects*; D012077:Renal Artery / Q000187:drug effects; D013045:Species Specificity
D011941:Receptors, Adrenergic; D002078:Butoxamine; D008790:Metoprolol; D007545:Isoproterenol