Histamine H₁- and H₂ receptors in pulmonary and systemic vasculature of the dog

This study was conducted to identify and clarify the actions of pulmonary and systemic H₁ and H₂ receptors by utilizing specific histamine receptor antagonists. Histamine was infused in anesthetized dogs during control conditions, after H₂ receptor blockade with metiamide, after H₁ receptor blockade with chlorpheniramine, and after combined H₁ and H₂ receptor blockade. Histamine infusion, alone, induced marked systemic vasodilatation, pulmonary vasoconstriction, and transient increases in cardiac output and heart rate. H₂ receptor blockade prevented the systemic vasodilatation and potentiated the pulmonary vasoconstriction induced by histamine. H₁ receptor blockade augmented the systemic vasodilatation, prevented the pulmonary vasoconstriction, and increased the cardiac output and heart rate responses induced by histamine. Thus, H₂ receptors appear to mediate the vasodilatation, tachycardia, and increased cardiac output induced by histamine, whereas H₁ receptors appear to mediate the vasoconstrictor and the minimal cardiac depressant actions of histamine. Histamine stimulates only H₁ and H₂ receptors, since combined H₁ and H₂ receptor antagonism prevented almost all of the cardiovascular actions of histamine.