Heterogenous effects of histamine on isolated rat coronary arteries.

The influence of increasing concentrations of histamine (0.1 microM-1 mM) was studied on proximal and distal ring segments of left anterior descendens coronary arteries isolated from rats. Addition of histamine to prostaglandin F2 alpha (10 microM)-precontracted proximal segments elicited a further contraction. This effect was endothelium-independent and mediated by a histamine H1 receptor mechanism since it was blocked by the histamine H1 receptor antagonist, mepyramine (10 microM), and not by the histamine H2 receptor antagonist, cimetidine (100 microM), and since it was mimicked by the histamine H1 receptor agonist, 2-pyridylethylamine, and not by the histamine H2 receptor agonist, dimaprit. Addition of histamine to prostaglandin F2 alpha-precontracted distal segments elicited concentration-dependent relaxation. This relaxation is histamine H2 receptor-mediated since it was blocked by cimetidine (100 microM) and not by mepyramine (10 microM) and since dimaprit but not 2-pyridylethylamine elicited relaxation. The relaxation was not due to the release of endothelial NO, prostaglandins or activation of ATP-regulated K+ channels since it was not inhibited by NG-nitro-L-arginine methyl ester (100 microM) or NG-nitro-L-arginine (100 microM), indomethacin (10 microM) or glibenclamide (10 microM). Our results show that the effects of histamine on rat left anterior descendens coronary arteries are heterogenous, depending on the relative location within the coronary vasculature and possibly, the relative preponderance of histamine H1 or H2 receptors on the smooth muscle cells.