Characterization of histamine-induced contraction in rat isolated aorta

Abstract

High concentrations of histamine (> 10 μM) 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 H 1-receptor antagonist, mepyramine (1 and 10 μM) and insensitive to the histamine H 2-receptor antagonist, cimetidine (10 μM), and to the cyclooxygenase inhibitor, indomethacin (5 μM). In contrast, the α-adrenoceptor antagonists, prasozin and pentholamine, antagonized these contractions in a concentration-dependent manner (respective apparent pK B values 9.7 and 7.9) and nifedipine (3 μM) 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 F 2α. This relaxation was abolished in the presence of mepyramine (1 μM). 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 (> 10 μM) are probably mediated by α 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.