Effect of Histamine Receptor Agonists and Antagonists on the Uterine Vasculature 1

Abstract

Histamine H₁ and H₂ receptors are known to exist in uterine smooth muscle; however, neither receptor has been clearly identified in the uterine vasculature. In the present study, 12 nonpregnant ewes were chronically instrumented with catheters in the carotid artery, jugular vein, uterine arteries, and electromagnetic flow probes on the uterine arteries for continuous measurement of uterine blood flow. Dose response curves were determined for bolus injections of Histamine (1-10 μg), the H₁ receptor agonist 2PEA (10-100 μg), and the H₂ receptor agonist Dimaprit (30-300 μg) before H₁ receptor blockade with pyrilamine, following H₁ receptor blockade, and following H₂ receptor blockade with metiamide. Uterine vasodilator responses to histamine and 2PEA were essentially abolished by pyrilamine, while responses to dimaprit were not altered. Following addition of metiamide, responses to histamine were reduced further and responses to dimaprit were abolished. Baseline uterine blood flow was not altered by either H₁ or H₂ receptor blockade or their combination. Intraarterial bolus injections of the mast cell histamine-releasing compound 48/80 (100-1000 μg) had no effect on uterine blood flow. These experiments demonstrate that the uterine vasculature of the ovine contains almost exclusively H₁ receptors, does not contain compound 48/80 sensitive mast cells and is not dependent upon endogenous histamine to maintain blood flow.