Identification and blockade of vascular H2 receptors.
Experiments were conducted in anesthetized dogs to determine the nature of receptors mediating vascular actions of histamine. In the perfused gracilis muscle histamine caused vasodilatation that was attenuated in part by mepyramine, an H1-receptor blocker. Metiamide, an H2 blocker, given alone had no effect on dilatation. However, the combination of mepyramine and metiamide resulted in a large attenuation of dilatation. Histamine caused constriction of the perfused saphenous vein that was totally blocked by mepyramine suggesting that venoconstriction by histamine involves only H1 receptors. Histamine infusion caused a fall in arterial pressure and a large reduction in peripheral resistance. Mepyramine attenuated the fall in pressure but not the reduction in resistance. Combined H1- and H2-receptor blockade largely eliminated the effects of histamine infusion further documenting the existence of H1 and H2 receptors. The effects of H1 and H2 antihistamines on a variety of physiological vasodilator responses were examined. Evidence was obtained to indicate that H1- and H2-histamine receptors are involved in the active component of baroreceptor-mediated reflex vasodilatation, poststimulation vasodilatation, sympathetic vasodilatation in the guanethidine-treated dog, and vasodilator responses following compound 48/80. No evidence for the participation of either H1- or H2-histamine receptors in reactive hyperemia or the dilatation accompanying exercise was found. It is concluded that in the dog both endogenously-released and exogenous histamine exert vascular effects by activation of both H1 and H2 receptors.
Identification and blockade of vascular H2 receptors. Experiments were conducted in anesthetized dogs to determine the nature of receptors mediating vascular actions of histamine. In the perfused gracilis muscle histamine caused vasodilatation that was attenuated in part by mepyramine, an H1-receptor blocker. Metiamide, an H2 blocker, given alone had no effect on dilatation. However, the combination of mepyramine and metiamide resulted in a large attenuation of dilatation. Histamine caused constriction of the perfused saphenous vein that was totally blocked by mepyramine suggesting that venoconstriction by histamine involves only H1 receptors. Histamine infusion caused a fall in arterial pressure and a large reduction in peripheral resistance. Mepyramine attenuated the fall in pressure but not the reduction in resistance. Combined H1- and H2-receptor blockade largely eliminated the effects of histamine infusion further documenting the existence of H1 and H2 receptors. The effects of H1 and H2 antihistamines on a variety of physiological vasodilator responses were examined. Evidence was obtained to indicate that H1- and H2-histamine receptors are involved in the active component of baroreceptor-mediated reflex vasodilatation, poststimulation vasodilatation, sympathetic vasodilatation in the guanethidine-treated dog, and vasodilator responses following compound 48/80. No evidence for the participation of either H1- or H2-histamine receptors in reactive hyperemia or the dilatation accompanying exercise was found. It is concluded that in the dog both endogenously-released and exogenous histamine exert vascular effects by activation of both H1 and H2 receptors.