The mechanism of histamine-induced relaxation in the isolated rat common carotid artery was analysed. Histamine (3 x 10(-7)-10(-4) mol/l) caused a concentration-dependent relaxation of the artery. Indomethacin, a cyclo-oxygenase inhibitor, and diethylcarbamazine, a lipoxygenase inhibitor, did not affect the relaxant response of the artery to histamine. After removal of the vascular endothelium the histamine-induced relaxation was strongly reduced. Moreover, hemoglobin and methylene blue, inhibitors of endothelium-derived relaxing factor (EDRF), prevented or reversed the relaxant effect of histamine. These findings confirm that the histamine-induced relaxation is to a greater extent endothelium dependent. It is concluded that the endothelium-dependent component in the relaxant response of the rat common carotid artery to histamine results from the release of EDRF.
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