Direct and indirect effects of histamine on the smooth muscle cells of the guinea-pig main pulmonary artery.

Electrophysiological studies of the effects of histamine on the smooth muscles in the guinea-pig main pulmonary artery revealed that this amine produced muscle contraction with an associated depolarization of the membrane. Application of cimetidine potentiated and that of mepyramine suppressed these histamine-induced responses. In the presence of mepyramine, histamine produced membrane hyperpolarization. Contractions produced by perivascular nerve stimulation were potentiated by histamine, and additional application of cimetidine further potentiated while addition of mepyramine suppressed the histamine-induced enhancement. The amplitude of excitatory junction potentials was increased by application of histamine plus cimetidine and was decreased by histamine plus mepyramine. Excitatory effects of histamine on the electrical and mechanical responses were reduced by application of tetrodotoxin, prazosin, phentolamine or guanethidine. In the presence of these drugs, histamine produced depolarization with an associated increase in membrane resistance and, in high concentrations, produced spike potentials. Electrical and mechanical responses of the smooth muscles to exogenously applied noradrenaline were potentiated by pretreatment with histamine and cimetidine, and were suppressed by histamine and mepyramine. These observations indicate that the guinea-pig main pulmonary artery possesses two types of histamine receptor, H1- and H2-receptors, in the smooth muscles and in the perivascular adrenergic nerves. Stimulation of H1 or H2-receptor produces excitatory or inhibitory effects, respectively, on the smooth muscles and on the adrenergic nerves. Contraction of the muscle tissues produced by histamine is brought about by a direct effect on the smooth muscles and by increased release of transmitters, as a result of excitation of perivascular nerves.