Chronic Nitric Oxide Synthase Inhibition Prevents New Coronary Capillary Generation

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Abstract
L-NAME-induced hypertension has been shown to produce concentric (eutrophic) remodeling of the heart despite an enhanced afterload. We postulated that nitric oxide synthase inhibition could limit coronary capillary growth to explain the nature of remodeling. To test our hypothesis, we aimed at determining the effect of endogenous and exogenous nitric oxide on coronary neovascularization. Aortic and coronary rings from normotensive animals were incubated in a three-dimensional type I collagen matrix in the presence of l-NAME or the nitric oxide donor SNAP. l-NAME inhibited, while SNAP stimulated, neovascularization from aortic and coronary rings after 12 days of in vitro incubation. In arterial rings harvested from rats treated with l-NAME for 14 days and in which no further in vitro treatment was added, only coronary rings showed a reduction in new capillary generation. While confirming that chronic l-NAME-treated rats develop concentric remodeling, the evaluation of capillary density did not reveal any difference as compared with the controls in 3 areas of the myocardium. In conclusion, chronic inhibition of nitric oxide synthesis in vivo produces a long-lasting reduction in the capacity of coronary arteries to generate new capillaries in vitro. Thus, our results lend support to the hypothesis that an inhibition of new capillary formation could prevent the development of compensatory ventricular hypertrophy, in favor of concentric remodeling.