IMPAIRMENT OF ENDOTHELIUM-DEPENDENT VASORELAXATION IN EXPERIMENTAL ATHEROSCLEROSIS IS DEPENDENT ON GENDER

Objective: Nitric oxide (NO) has been suggested to have antiatheroscle rotic effects. It has also been demonstrated that there is a greater b asal release of endothelium derived relaxing factor (EDRF) in female a s compared to male rabbit aorta, which also might have beneficial effe cts in atherosclerosis. We thus sought to determine if gender influenc es the severity of atherosclerosis. Methods: We studied 18 female and 18 male New Zealand White rabbits that were randomly divided in two gr oups of 9 animals each and fed either a standard or a cholesterol diet (0.75%) for 15 weeks. Results: In cholesterol-fed rabbits the percent age of atherosclerotic lesions in the aorta was identical in females a nd males and was inversely correlated with the maximal aortic relaxati on to acetylcholine as assessed in organ chamber experiments (females P < 0.0008, males: P <0.0002). Importantly, the cholesterol diet induc ed a significantly (P < 0.025) more severe impairment of maximal vasor elaxation to acetylcholine in males from 78.4 +/- 1.2% to 29.4 +/- 10. 2%) compared to females (from 84.4 +/- 1.2% to 60.7 +/- 8.5%). Both ma le gender (P < 0.0001) and the extent of impairment of endothelium-dep endent relaxation(P < 0.0002) were associated with a reduced aortic se nsitivity to S-nitroso-N-acetyl-D,L-penicillamine, which releases NO i nto the organ bath. In contrast, the aortic sensitivity to the organic nitrates pentaerythritol tetranitrate and isosorbide 5-nitrate, which release NO after enzymatic metabolization within the smooth muscle, w as not reduced. Conclusions: These results suggest that the impairment of endothelium-dependent vasorelaxation induced by atherosclerosis is dependent on gender. This may be due to a greater degradation of extr acellular NO in the vessel wall of males. (C) 1998 Elsevier Science B. V.