PT - JOURNAL ARTICLE AU - R J Winquist AU - P B Bunting AU - T L Schofield TI - Blockade of endothelium-dependent relaxation by the amiloride analog dichlorobenzamil: possible role of Na+/Ca++ exchange in the release of endothelium-derived relaxant factor. DP - 1985 Dec 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 644--650 VI - 235 IP - 3 4099 - http://jpet.aspetjournals.org/content/235/3/644.short 4100 - http://jpet.aspetjournals.org/content/235/3/644.full SO - J Pharmacol Exp Ther1985 Dec 01; 235 AB - The importance of extracellular calcium for the expression of endothelium-dependent relaxation was examined in isolated rat aortic rings contracted by methoxamine. The endothelium-dependent relaxation generated by acetylcholine or the calcium ionophore A23187 was eliminated when rings were placed in physiological buffer to which calcium had not been added. The endothelium-independent relaxation to sodium nitroprusside was still elicited in the presence of this "low calcium" buffer. Pretreatment of aortic rings with high concentrations of nifedipine (5 X 10(-7) M) or verapamil (10(-5) M) caused a comparable displacement to the right (2-3 times) in the relaxant dose-response curve for acetylcholine, A23187 and sodium nitroprusside with little or no changes in the maximal relaxation obtained with these vasodilators. Increasing concentrations of dichlorobenzamil, an analog of amiloride and a recently described inhibitor of calcium influx via sodium-calcium exchange, functionally antagonized and abolished the relaxations elicited by acetylcholine and A23187, but had no appreciable effect on the relaxations to sodium nitroprusside or atrial natriuretic factor (an endothelium-independent vasodilator). Similar results were obtained using isolated rabbit aortic rings. Thus, although the presence of extracellular calcium is critically required for the expression of endothelium-dependent relaxation, the associated calcium translocation is not blocked by the organic calcium entry blockers. The results with dichlorobenzamil suggest that sodium-calcium exchange may be an important mechanistic step in the release of endothelium-derived relaxant factor.