Different contribution of endothelial nitric oxide in the relaxation of human coronary arteries of ischemic and dilated cardiomyopathic hearts

Coronary artery disease and congestive heart failure (CHF) have been associ ated with a. reduction in nitric oxide (NO) release or bioavailability from the vascular endothelium. The objectives of this study were to compare the role of NO in human coronary vessels isolated from nonischemic dilated (DC M) (n = 10) and ischemic (ICM) (n = 12) cardiomyopathic hearts. Segments we re mounted on a wire myograph to record changes in isometric tension, All e xperiments were performed in the presence of indomethacin (10 muM). Contrac tions induced by angiotensin II (0.1 muM) or a depolarizing physiologic sol ution containing 40 mM KCl, were of similar amplitude in DCM and ICM. In ve ssels precontracted with angiotensin II, acetylcholine (1 muM) caused an en dothelium-dependent relaxation of rings from DCM but a paradoxical contract ion of rings from ICM; NO synthase inhibition with N-omega-nitro-L-arginine (L-NNA, 100 muM) did not affect acetylcholine-induced relaxation or contra ction of DCM or ICM vessels, respectively. By contrast, substance P (0.1 mu M) induced an endothelium-dependent relaxation in both groups of vessels; t his relaxation was prevented (p < 0.05) by L-NNA in vessels from ICM hearts but only reduced (p < 0.05) by L-NNA in vessels from DCM hearts. In depola rized conditions, acetylcholine contracted (p < 0.05) whereas substance P i nduced a complete relaxation (p < 0.05) of vessels from both groups; substa nce P-induced relaxation was abolished (p < 0.05) by L-NNA, Our data sugges t that in the presence of indomethacin, NO does not contribute to acetylcho line-induced relaxation of human epicardial coronary arteries isolated from DCM hearts. Furthermore, whereas NO and a secondary endothelium-derived re laxing factor sensitive to high K+ contribute to substance P-induced relaxa tion of rings from DCM hearts, only NO is involved in ICM hearts.