Vasodilator response to histamine: dependence upon the site of administration

Histamine causes vasodilation in part by interacting with histamine H2 receptors. The present study was undertaken to evaluate the difference in vasodilator sensitivity of H2 receptors on the inside compared to the outside of the vessel. In order to induce tone, norepinephrine was administered to an in vitro preparation of rabbit ear artery treated with mepyramine to block H1 receptors. Histamine was then either selectively perfused through the artery or added to the outside of the vessel via the organ bath. The outside of the artery was found to be twice as sensitive to the vasodilator effect of histamine as the inside. These data provide the first evidence for greater extraluminal sensitivity of vascular smooth muscle and suggest that the response to histamine will depend in part on the route the amine takes to reach receptors, e.g., from blood-borne sources or from extraluminal stores.