CHRONIC NITRIC-OXIDE INHIBITION AS A MODEL OF HYPERTENSIVE HEART-MUSCLE DISEASE

We have compared the myocardial alterations in rats made hypertensive by the chronic inhibition of nitric oxide biosynthesis with those havi ng renal hypertension (two kidney-one clip model), Male Wistar rats we re chronically administered the nitric oxide synthase inhibitor N-omeg a-nitro-L-arginine methyl ester (L-NAME) for 2, 4 and 8 weeks. Both gr oups initially developed a similar increase in blood pressure but only the 2K-1C rats developed myocardial hypertrophy after 2-4 weeks. L-NA ME-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 fib rosis and myocardial necrosis: especially in regions of the subendocar dium. The histological alterations induced by L-NAME were not caused b y the accompanying hypertension, since the 2K-1C animals had a similar increase in arterial blood pressure without any significant alteratio ns 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 altera tions. Animals which received the inactive enantiomer D-NAME did not d evelop hypertension nor did they have any morphological abnormalities. Both the coronary flow and the contractile capacity of hearts isolate d from rats treated viiith L-NAME for 8 weeks were impaired compared t o control animals. These results indicate that the chronic inhibition of NO biosynthesis causes cardiac ischemia associated with a mechanica l dysfunction that is unrelated to cardiac hypertrophy which is simila r to those seen in some patients suffering from chronic arterial hyper tension.