Influence of the Endothelium on Histamine-Induced Relaxation of Rat Middle Cerebral Arteries in Vitro

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Abstract
Histamine relaxed PGF2-precontracted rat isolated middle cerebral arteries (ID 230 μm) concentration dependently with a pD2 of 5.31 (EC50: 5 x 10-6M). Cimetidine induced a concentration-dependent rightward shift of the histamine concentration-response curve of endothelium-intact arteries. The slope of the Schild plot was indistinguishable from unity, and the estimated pA2 for cimetidine was 6.14. The selective H2-receptor agonist dimaprit induced a concentration dependent relaxation of the cerebral arteries similar to that induced by histamine. This indicates that the histamine receptor mediating the relaxation in rat middle cerebral arteries belongs to the H2-receptor subtype. 2-Pyridylethylamine, a selective H1-receptor agonist, induced a small concentration-dependent cotraction of the arteries with a pD2 of 4.16. Mepyramine, a selective H3-receptor antagonist had no potentiating effect on the relaxation induced by histamine, suggesting either that the contractile effect of 2-pyridylethylamine is nonselective or that H1 receptors mediating contraction are of minor importance for the overall histamine response. The selective H3-receptor agonist. (R)-α-methylhistamine, was without effect in a specific concentration range (10-7-10-5M) excluding participation of H3 receptors in the histamineinduced relaxation of these vessels. Indomethacin did not affect the vessel response to histamine. but removal of the endothelium and treatment of endothelium-intact arteries with 3 x 10-6M methylene blue induced a similar 0.5 log rightward shift of the histamine concentration response curve. The results indicate that histamine induces relaxation of rat middle cerebral arteries by activating primarily H2 receptors. causing indirect relaxation of the arteries by endothelium-derived relaxing factor (EDRF) release and directly through activation of H2 receptors on the vascular smooth muscle.

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