Chronic disturbances in NO production results in histochemical and subcellular alterations of the rat heart

The mechanisms and myocardial alterations associated with NO-deficient hype rtension are still far from clear. The aim of the present study was to focu s on the enzyme histochemical and subcellular changes in the heart of L-NAM E, treated rats, as well as to examine the influence of captopril treatment . Wistar rats were administered either L-NAME (40 mg/kg/day) alone ol toget her with captopril (100 mg/kg/day) for a period of 4 weeks. 4 significant i ncrease or blood pressure confirmed the reliability of the model. The resul ts showed that long-lasting L-NAME administration was accompanied by a decr ease of endothelial NO-synthase activity and by a significant local decreas e of the following enzyme activities: capillary-related alkaline phosphatas e. 5'-nucleotidase and ATPase (but not dipeptidyl peptidase IV) and cardiom yocyte-related glycogen phosphorylase, succinic dehydrogenase, beta-hydroxy butyrate dehydrogenase and ATPases. No activity of these enzymes was found in rile scar, whereas a marked increase of alkaline phosphatase and dipepti dyl peptidase IV activities was found in the foci of fibrotization. Histoch emical changes correlated with subcellular changes, which were characterize d by 1) apparent fibroblast activation associated with interstitial/perivas cular fibrosis. 2) heterogeneous population of the hypertrophic and injured cardiomyocytes 3) enhancement of the atrial granules and their translocati on into the sarcolemma, and 4) impairment of capillaries as well as by indu ction of angiogenesis. Similar alterations were also found in the heart of captopril co-treated rats, despite of the significant suppression of blood pressure. The results indicate that NO-deficient hypertension is accompanie d by metabolic disturbances and ultrastructural alterations of the heart an d these changes are probably not induced by the I renin-angiotensin system only.