Inhibition of cardiac sympathetic neurotransmission by histamine in the dog is mediated by H1-receptors.
1 The role of histamine H1- and H2-receptors in mediating prejunctional inhibition of cardiac sympathetic neurotransmission and histamine-induced coronary vasodilatation were investigated in perfused dog hearts in situ. 2 Intra-arterial injections of histamine into the right coronary artery during the resting state caused slightly positive chronotropic responses in doses larger than 1 microgram. 3 Histamine in doses of 0.1 to 10 micrograms into the right coronary artery reduced the tachycardia resulting from electrical stimulation of the cardiac sympathetic nerves. 4 Intra-coronary infusions of chlorpheniramine (300 micrograms/min) significantly reduced the histamine-induced depression of cardiac nerve stimulation. The effects of cimetidine (300 micrograms/min) and metiamide (300 micrograms/min) were less pronounced. 5 Histamine (1 to 10 micrograms) further increased heart rate resulting from the continuous intra-coronary infusion of noradrenaline (1 or 3 micrograms/min). 6 Intra-arterial injections of histamine (0.1 to 10 micrograms) caused an increase in coronary blood flow in a dose-dependent manner. This was partially inhibited by intra-coronary infusion of chlorpheniramine (10 to 300 micrograms/min) and by cimetidine (10 to 300 micrograms/min). The combination of both drugs (10 to 100 micrograms/min of each) caused a larger inhibition. 7 The present results suggest that the histamine-induced depression of heart rate during cardiac sympathetic nerve stimulation is due to a prejunctional effect mediated mainly by H1-receptors. Histamine-induced coronary vasodilatation in the dog is mediated both by H1- and H2-receptors.
D000818:Animals; D002744:Chlorpheniramine / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000294:innervation; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects / Q000294:innervation*; D006339:Heart Rate / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology*; D008297:Male; D008785:Metiamide / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011968:Receptors, Histamine / Q000187:drug effects*; D011969:Receptors, Histamine H1 / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects
D011968:Receptors, Histamine; D011969:Receptors, Histamine H1; D008785:Metiamide; D002744:Chlorpheniramine; D002927:Cimetidine; D006632:Histamine; D009638:Norepinephrine