Chronic inhibition of nitric oxide synthase induces hypertension and cardiornyocyte mitochondrial and myocardial collagen remodelling in the absence of hypertrophy

Objectives To evaluate the morphometric and ultrastructural alterations of the heart produced by long-term inhibition of nitric oxide (NO) synthase with N-omega-nitro-(L)-arginine methyl ester (L-NAME) and to examine whether the changes are caused by L-NAME-induced hypertension or a lack of NO. Methods Male Wistar rats were divided randomly into three sets: control group, standard diet/(L)-NAME-treated group, and standard diet/(L)-NAME + captopril-treated group. Results Chronic inhibition of NO synthesis with (L)-NAME given for 4 weeks promoted a time-dependent hypertensive response which was not accompanied by an increase in cardiac mass, myocellular hypertrophy or other evidence of myocyte damage. However, this response was associated with left ventricular cardiomyocyte mitochondrial remodelling and discrete interstitial fibrosis in both the left and right ventricles. The remodelling was characterized by an increase in the number and size of mitochondria. Importantly, systolic pressure overload did not result in left ventricle decompensation. The concomitant treatment with L-NAME and captopril abolished the development of hypertension and left ventricular cardiomyocyte subcellular remodelling, but not the discrete interstitial fibrosis in the left and right ventricle. Conclusions The present study suggests that, in the (L)-NAME model of hypertension, decreased NO production could be an important means of controlling cardiovascular hypertensive stress by regulating mitochondrial biogenesis and function in the tissue. On the other hand, discrete interstitial ventricular myocardial fibrosis observed in (L)-NAME-treated rats, either hypertensive or rendered normotensive with captopril, clearly indicates that this response depends on a process associated with NO insufficiency. (C) 2003 Lippincott Williams Wilkins.