Presynaptic inhibition by histamine of cardiac sympathetic neurotransmission in dogs.

Abstract

The role of histamine H1 and H2-receptors in mediating presynaptic inhibition of cardiac sympathetic neurotransmission and histamine-induced coronary vasodilatation were studied in perfused dog hearts in situ. Histamine (0.1 to 10 μg) into the right coronary artery reduced tachycardia resulting from electrical stimulation of the cardiac sympathetic nerves. Intra-coronary infusions of chlorpheniramine (300 μg/min) reduced the histamine-induced depression of cardiac sympathetic nerve stimulation. The effects of Cimetidine (300 μg/min) and metiamide (300 yg/min) were less pronounced. Histamine (1 to 10 μg) caused slightly positive chronotropic responses during resting state and further increased heart rate resulting from the continuous intra-coronary infusion of norepinephrine (1 or 3 μg/min). Intra-arterial injections of histamine (0.1 to 10 μg) caused increase in coronary blood flow. This was partially inhibited by intra-coronary infusion of chlorpheniramine (10 to 300 μg/min) and by Cimetidine (10 to 300 μg/min). The combination of both drugs caused a larger inhibition. The present results suggest that the histamine-induced depression of heart rate during cardiac sympathetic nerve stimulation is due to a presynaptic effect mediated mainly by H1-receptors. Histamine-induced coronary vasodilatation is mediated both by H1- and H2-receptors.