Abstract
To investigate if the increased responsiveness to norepinephrine observed in uremia could be due to a humoral factor present in uremic human serum, contractions elicited by norepinephrine in rings of rat thoracic aortas with or without endothelium were obtained in the absence or presence of normal or uremic human sera. In addition cumulative concentration–effect curves to acetylcholine and sodium nitroprusside were constructed in precontracted aortas with or without endothelium in the absence or presence of uremic human serum. Sera obtained from healthy subjects did not modify the contraction elicited by norepinephrine whereas uremic serum enhanced norepinephrine effect in preparations with or without endothelium. The enhanced effect to norepinephrine was further potentiated in preparations with endothelium pretreated with indomethacin or methylene blue. Indomethacin abolished and methylene blue did not alter the potentiation to norepinephrine induced by uremic sera in preparations without endothelium. Uremic human serum did not modify the relaxant effect of acetylcholine or sodium nitroprusside obtained in preparations precontracted with norepinephrine. The present data suggest that serum from uremic patients contain factor(s) that alter the reactivity of vascular smooth muscle by a mechanism that involves the cycloxygenase pathway as well as an increase in EDRF release.