Electrical membrane events in response to alpha-adrenoceptor stimulation.

Strips of rabbit main pulmonary artery (RMPA) were used to study the effects of several agonists on tension development and membrane potential of the vascular smooth muscle cells. The following alpha-adrenoceptor agonists were employed: methoxamine and St 587 (alpha 1-selective), B-HT920 (alpha 2-selective) and clonidine, which stimulates preferentially alpha 2-adrenoceptors. By the use of the selective antagonists prazosin and yohimbine it was not possible to differentiate convincingly between alpha 1- and alpha 2-adrenoceptors in the RMPA. Methoxamine and B-HT920 produced depolarization of similar magnitude of the membrane of the vascular smooth muscle cells. In spite of these results, which point to a uniform alpha-adrenoceptor in the RMPA, contractions to alpha 1- and alpha 2-agonists differed in some important aspects. Contractions in response to alpha 2-agonists were highly susceptible to the inhibitory effects of calcium withdrawal and calcium antagonists whereas contractions to alpha 1-agonists were much less so. Reduction of the membrane potential of the vascular cells by K+ at 12 mmol/l had no effect on the concentration-contraction curve of methoxamine but shifted that of B-HT920 to the left. Conversely hyperpolarization of the membrane of the vascular smooth muscle cells by strychnine totally suppressed contraction to B-HT920 and caused only a rightward shift of the concentration-contraction curve of methoxamine and St 587. Interaction of alpha 1- and alpha 2-agonists with an apparently uniform alpha-adrenoceptor induces in the RMPA contraction which seems to be triggered by different membrane processes.