Chronic nitric oxide inhibition as a model of hypertensive heart muscle disease

FAPESP – FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ – CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOWe have compared the myocardial alterations in rats made hypertensive by the chronic inhibition of nitric oxide biosynthesis with those having renal hypertension (two kidney-one clip model), Male Wistar rats were chronically administered the nitric oxide synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) for 2, 4 and 8 weeks. Both groups initially developed a similar increase in blood pressure but only the 2K-1C rats developed myocardial hypertrophy after 2-4 weeks. L-NAME-treated animals developed a similar degree of hypertrophy following 8 weeks of treatment, As observed by light microscopy, the myocardial alterations in the latter animals consisted of extensive areas of fibrosis and myocardial necrosis: especially in regions of the subendocardium. The histological alterations induced by L-NAME were not caused by the accompanying hypertension, since the 2K-1C animals had a similar increase in arterial blood pressure without any significant alterations in the heart morphology. 2K-1C rats treated chronically with L-NAME behaved in a manner similar to the L-NAME-treated animals with regard to both the blood pressure increases and cardiac morphological alterations. Animals which received the inactive enantiomer D-NAME did not develop hypertension nor did they have any morphological abnormalities. Both the coronary flow and the contractile capacity of hearts isolated from rats treated viiith L-NAME for 8 weeks were impaired compared to control animals. These results indicate that the chronic inhibition of NO biosynthesis causes cardiac ischemia associated with a mechanical dysfunction that is unrelated to cardiac hypertrophy which is similar to those seen in some patients suffering from chronic arterial hypertension913248255FAPESP – FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ – CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP – FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ – CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGIC