Impairment of endothelium-dependent vasorelaxation in experimental atherosclerosis is dependent on gender.

OBJECTIVE: Nitric oxide (NO) has been suggested to have antiatherosclerotic effects. It has also been demonstrated that there is a greater basal release of endothelium derived relaxing factor (EDRF) in female as compared to male rabbit aorta, which also might have beneficial effects in atherosclerosis. We thus sought to determine if gender influences the severity of atherosclerosis. METHODS: We studied 18 female and 18 male New Zealand White rabbits that were randomly divided in two groups of 9 animals each and fed either a standard or a cholesterol diet (0.75%) for 15 weeks. RESULTS: In cholesterol-fed rabbits the percentage of atherosclerotic lesions in the aorta was identical in females and males and was inversely correlated with the maximal aortic relaxation to acetylcholine as assessed in organ chamber experiments (females: P < 0.0008, males: P < 0.0002). Importantly, the cholesterol diet induced a significantly (P < 0.025) more severe impairment of maximal vasorelaxation 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 male gender (P < 0.0001) and the extent of impairment of endothelium-dependent relaxation (P < 0.0002) were associated with a reduced aortic sensitivity to S-nitroso-N-acetyl-D,L-penicillamine, which releases NO into 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, was 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 extracellular NO in the vessel wall of males.

Comparison of the vasorelaxing effect of different nitrovasodilators in conductive arterial and venous blood vessels.

We tested classically used organic nitrovasodilators such as s-nitroso-n-acetyl-D,L-penicillamine, 3-morpholino-sydnonimine, pentaerythrityl-tetranitrate, isosorbide-dinitrate, isosorbide-mononitrate, glyceryl-trinitrate on different isolated conductive arterial and venous blood vessels of the same species (rabbit). We found an up to two orders of magnitude more pronounced venoselectivety in the systemic-circulation as compared to the lung-circulation. ISMN and PETN were most venoselective nitrovasodilators, with PETN being the most potent drug in all vessels studied.