Histamine releases PGI2 from human pulmonary artery

Abstract Histamine caused a triphasic response of human pulmonary artery strips in vitro, consisting of a small initial contraction followed by pronounced relaxation preceding a second contractile response. These characteristics were not seen with other contractile stimuli including 5-hdyroxytryptamine, leukotriene D 4 , and KC1. The relaxant component of this response was ablated by removal of endothelium from the vascular strips or by pretreatment of the tissues with 1μM indomethacin. Measurement of the PGI 2 degradation product 6-keto-PGF 1α in supernatants from histamine-challenged tissues confirmed the synthesis of PGI 2 . Supernatants from unstimulated or leukotriene-challenged tissues contained no detectable amounts of 6-keto-PGF 1α . The histamine H 1 antagonist diphenhydramine inhibited both the contractile and relaxant responses to histamine whereas the H 2 antagonist cimetidine affected neither component. The released PGI 2 significantly altered the dose-respons curve to histamine without inhibiting the maximal contractile responses. We conclude that histamine induces PGI 2 formation from pulmonary arterial endothelium via an H 1 receptor.