Differential inhibitory effects of nitroglycerin on contractile responses to the alpha-adrenoceptor agonists, methoxamine and clonidine, in rabbit aorta.
The vasoinhibitory action of nitroglycerin was examined on contractile responses to methoxamine and clonidine in isolated rabbit aorta. Nitroglycerin at 10(-5) M, but not 10(-6)-10(-8) M, shifted the concentration response curve for methoxamine to the right. Nitroglycerin (10(-8)-10(-5) M), however, noncompetitively inhibited responses to clonidine in a concentration dependent manner. Nitroglycerin (10(-5) M) had no effect on responses to potassium (10-70 mM), but slightly inhibited responses to Ca2+ (0.1-5 mM) in a Ca2+-free medium containing potassium. Nifedipine (10(-6) and 10(-5) M), however, almost abolished responses to both potassium and Ca2+ but had no effect on responses to either methoxamine or clonidine. Agonist-antagonist interactions using prazosin and yohimbine revealed that responses to both methoxamine and clonidine were due to activation of alpha 1-adrenoceptors. Results with phenoxybenzamine suggested that the aorta has more receptor reserve for methoxamine than for clonidine. Furthermore, in tissues pretreated with phenoxybenzamine, nitroglycerin (10(-5) M) inhibited the maximal contractile response to methoxamine (3 x 10(-4) M). The maximal response to clonidine in tissues pretreated with phenoxybenzamine was not affected by nitroglycerin (10(-8) M). Nitroglycerin (10(-9)-10(-4) M) had greater inhibitory effect on residual responses to clonidine (10(-5) M) than that to methoxamine (10(-5) M) in a Ca2+-free medium containing EGTA. The contractile responses to Ca2+ (2 mM) in a Ca2+-free medium containing EGTA, nifedipine, and either methoxamine (5 x 10(-7) M) or clonidine (3 x 10(-7) M) were inhibited by nitroglycerin (10(-9) - 10(-5) M). The effect of nitroglycerin was greater on responses in the presence of clonidine than methoxamine.(ABSTRACT TRUNCATED AT 250 WORDS)
Shibata
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S
Department of Pharmacology, School of Medicine, University of Hawaii, Honolulu 96822.
Satake
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N
Hester
R K
RK
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002132:Calcium Radioisotopes; D003000:Clonidine / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007811:Lanthanum; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology*; D010643:Phenoxybenzamine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011817:Rabbits; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D002132:Calcium Radioisotopes; D010643:Phenoxybenzamine; D015016:Yohimbine; D004533:Egtazic Acid; D007811:Lanthanum; D005996:Nitroglycerin; D008729:Methoxamine; D009543:Nifedipine; D003000:Clonidine; D011188:Potassium; D002118:Calcium; D011224:Prazosin