Evidence for Presynaptic Inhibitory Histamine (H2) Receptors in the Rat Hindquarter Vasculature

Abstract

Histamine released within walls of resistance blood vessels is suggested to mediate an active portion of baroreceptor-mediated neurogenic vasodilatation in skeletal muscle vasculature. Studies were undertaken to examine the possibility that histamine-mediated active vasodilatation could be effected, in part, by an inhibitory presynaptic action of histamine on vascular sympathetic varicosities. All experiments were conducted in constant-flow autoperfused rat hindquarters in which vasoconstrictor responses were evoked by sympathetic chain (L2-4) stimulation at varying frequencies or intraarterial norepinephrine (0.5 microgram) administration. Intraarterial histamine infusion resulted in a significant inhibition of nerve-stimulated hindquarter vasoconstriction, with the greatest reduction (20%) occurring at the 82.5-ng/ml/min dose. The inhibitory effect of histamine was not stimulation frequency dependent, and occurred when the vasoconstrictor responses to intraarterial norepinephrine and dilator responses to intraarterial nitroglycerin (1 microgram) were unaltered by the histamine infusions. The H2 agonist impromidine produced a significant inhibition of nerve-stimulated hindquarter vasoconstrictor responses without altering perfusion pressure responsiveness to either intraarterial norepinephrine or nitroglycerin. The magnitude of this inhibition of nerve-stimulated vasoconstrictor response was equivalent to or greater than that produced by histamine. The alpha 2-agonist clonidine produced a significant inhibitory effect on neurogenic vasoconstrictor responses with a maximum of 54%. Cimetidine infusion (10 mg/kg i.a.) essentially abolished the inhibitory effect of histamine on nerve-stimulated hindquarter vasoconstriction. These results are consistent with the existence of inhibitory presynaptic histamine receptors on sympathetic varicosities in the hindquarter vascular bed. Furthermore, evidence supports these inhibitory receptors being of the H2 class and the possibility that histamine-mediated active vasodilatation in rat hindquarters involves inhibitory presynaptic histamine receptors.