Differential inhibitory effects of nitroglycerin on contractile responses to the α-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.