EVIDENCE THAT HISTAMINE IS INVOLVED AS A MEDIATOR OF ENDOTHELIUM-DEPENDENT CONTRACTION INDUCED BY A23187 IN BOVINE INTRAPULMONARY VEIN

This study was initiated to test the hypothesis that histamine can act as an endothelium-derived contracting factor in bovine isolated intra pulmonary vein. The effects of calcium ionophore, calcimycin (A23187), on isometric tension were compared in unstimulated rings of intrapulm onary vein with and without endothelium. A23187 (0.1-10 mu M) induced concentration-related contraction when endothelium was present. Destru ction of endothelium markedly inhibited A23187-induced contraction. Me thylene blue, hemoglobin or N-G-methyl-L-arginine significantly enhanc ed A23187-induced contraction only in venous rings with endothelium co nsistent with attenuation of the contraction by the concomitant releas e of endothelium-derived relaxing factor (nitric oxide) [EDRF(NO)]. Hi stamine H-1 receptor antagonists inhibited, and iproniazid enhanced, c ontraction elicited by A23187. A23187 induced release of greater amoun ts of histamine from venous rings with than without endothelium. A2318 7-induced contraction was not mimicked by the mast cell activator, com pound 48/80, and was not inhibited by preexposure to compound 48/80 or in the presence of cromolyn or doxantrazole. A23187-induced contracti on was not inhibited by pretreatment with indomethacin, phentolamine, lipoxygenase inhibitors or superoxide dismutase. The results indicate that A23187 induces endothelium-dependent contraction in bovine intrap ulmonary vein and support histamine as one major mediator involved. Th e association of destruction of endothelium with an inhibition of both A23187-induced contraction and histamine release is consistent with t he endothelium as a source for histamine which can exert a local vasoc onstrictor effect in bovine intrapulmonary vein.