Prejunctional histamine H-3-receptors inhibit electrically evoked endogenous noradrenaline overflow in the portal vein of freely moving rats

The effects of intra-arterial injection of different doses of the selective histamine H-3-receptor agonist R-alpha-methylhistamine and the selective histamine H-3-receptor antagonist thioperamide on basal and electrically evoked noradrenaline overflow in the portal vein as well as on mean arterial pressure (MAP) and heart rate (HR) were investigated in permanently instrumented freely moving rats. R-alpha-Methylhistamine (0.01, 0.1 and 1 mu mol/kg) inhibited the evoked noradrenaline overflow up to 43%, the ED(50) value being 0.013 mu mol/kg. Thioperamide (0.1, 0.5 and 1.0 mu mol/kg) antagonized the effect of 1.0 mu mol/kg R-alpha-methylhistamine dose-dependently, evoked overflow returning to control values at 1.0 mu mol/kg of the antagonist; thioperamide alone had no effect on electrically evoked noradrenaline overflow. Basal noradrenaline levels, blood pressure and heart rate were not at all influenced by R-alpha-methylhistamine and thioperamide, alone or in combination. The results clearly show the presence of prejunctional histamine H-3-receptors inhibiting the electrically evoked noradrenaline overflow from vascular sympathetic nerve terminals in the portal vein of freely moving rats.