Characterization of histamine-induced contraction in rat isolated aorta

High concentrations of histamine (greater than 10 microM) contract rat aortic rings and the effect is greatly enhanced when the endothelium is removed. The present study was aimed at characterizing the histamine-induced contractions of de-endothelialized rat aortic rings. These contractions were poorly inhibited by the histamine H1-receptor antagonist, mepyramine (1 and 10 microM) and insensitive to the histamine H2-receptor antagonist, cimetidine (10 microM), and to the cyclooxygenase inhibitor, indomethacin (5 microM). In contrast, the alpha-adrenoceptor antagonists, prasozin and pentholamine, antagonized these contractions in a concentration-dependent manner (respective apparent pKB values 9.7 and 7.9) and nifedipine (3 microM) reduced them by about 75%. Pretreatment of de-endothelialized rings with 8-bromo-cyclic GMP and of intact rings with methylene blue resulted in respective inhibition and enhancement of histamine-induced contractions, quite similarly to the effects in the presence and in the absence of endothelium, respectively. Histamine elicited endothelium-dependent relaxation of aortic rings precontracted by prostaglandin F2 alpha. This relaxation was abolished in the presence of mepyramine (1 microM). However, mepyramine failed to mimic the enhancing effect of endothelium removal on histamine-induced contractions of resting aortic rings. It is concluded that, in rat aorta, (1) contractions induced by high concentrations of histamine (greater than 10 microM) are probably mediated by alpha 1-adrenoceptors; and (2) spontaneous, but not histamine-stimulated, release of endothelium-derived relaxing factor is mainly involved in the modulation of histamine-induced contractions.