DILATING EFFECT OF HISTAMINE ON PIAL ARTERIES OF CATS AND ITS MEDIATION BY H-2 RECEPTORS

We studied the effect of histamine and H1 or H2 blockers on the diameter of pial arteries (39-227 μm) using microapplication into the perivascular space. Concentration-response curves for histamine showed dilations which started at 10-7 M and were maximal at 10-5 and 10-4 M. The H2 blocker, cimetidine, induced no vascular reaction over the whole concentration range tested (10-7 to 10-3 M). The H1 blocker, mepyramine, was not vasoactive in the concentration range from 10-7 to 5x10-5 M and evoked dilations at higher concentrations. The concentration-response curve for histamine was only slightly displaced by 10-5 M mepyramine but was significantly shifted to the right by 10-5 M cimetidine. The dilating effect of histamine could be reduced in a stepwise manner by increasing concentrations of cimetidine. These findings are in accordance with a selective antagonism between histamine and cimetidine at the H2 receptors of smooth muscle cells of pial arteries. The insignificant role of H1 receptors in histamine-induced dilations is supported by the finding that a combination of H1 and H2 blockers resulted in the same reduction of histamine-induced dilation as did the application of the H2 blocker.