The dilating effect of histamine on pial arteries of cats and its mediation by H2 receptors.

We studied the effect of histamine and H1 or H2 blockers on the diameter of pial arteries (39-227 micron) 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 5 X 10(-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.