In vivo demonstration of H3-histaminergic inhibition of cardiac sympathetic stimulation by R-a-methyl-histamine and its prodrug BP 2.94 in the dog

Abstract

1 The aim of this study was to investigate whether histamine H3-receptor agonists could inhibit the effects of cardiac sympathetic nerve stimulation in the dog. 2 Catecholamine release by the heart and the associated variation of haemodynamic parameters were measured after electrical stimulation of the right cardiac sympathetic nerves (1-4 Hz, 10 V, 10 ms) in the anaesthetized dog treated with R-a-methyl-histamine (R-HA) and its prodrug BP 2.94 (BP). 3 Cardiac sympathetic stimulation induced a noradrenaline release into the coronary sinus along with a tachycardia and an increase in left ventricular pressure and contractility without changes in mean arterial pressure. Intravenous administration of H3-receptor agonists significantly decreased noradrenaline release by the heart (R-HA at 2 /imol kg-1 h~1 : +77 + 25 vs +405±82; BP 2.94 at 1 mg kg-1: +12±11 vs +330+100 pg ml-1 in control conditions, P<0.05), and increases in heart rate (R-HA at 2/imol kg-1 h1 : +26 + 8 vs +65+10 and BP 2.94 at 1 mgkg-1: +30 + 8 vs 75 + 6 beats min-1, in control conditions P<0.05), left ventricular pressure, and contractility. Treatment with SC 359 (1 mg kg-1) a selective H3-antagonist, reversed the effects of H3-receptor agonists. Treatment with R-HA at 2 /mol kg-1 h-1 and BP 2.94 at 1 mg kg-1 tended to decrease, while that with SC 359 significantly increased basal heart rate (from 111±3 to 130 + 5 beats min-1, PO.OOl). 4 Functional Hj-receptors are present on sympathetic nerve endings in the dog heart. Their stimulation by R-a-methyl-histamine or BP 2.94 can inhibit noradrenaline release by the heart and its associated haemodynamic effects. © 1999 Stockton Press All rights reserved.