Background: A chronic NO deficiency occurs under several physiological and pathophysiological conditions. The reduction in NOS activity during heart failure or chronic renal insufficiency must also be considered, such as the reduced NO levels in postmenopausal women. On the other hand, a chronic decrease in NO is considered responsible for a variety of cardiovascular diseases. There is evidence that chronic NO deficiency contributes to increased matrix deposition and fibrosis. The current study investigates to what extent chronic NO deficit affects the cardiac deposition of extracellular matrix in the left (LV) and right (RV) ventricle. Methods: NO deficit was achieved in adult rats by feeding them the NO-synthase-inhibitor L-NAME alone (L) and in combination with hydralazine (L/H) or captopril (L/C) (n=8 each group). Heart weight to body weight ratio, the expression of fibrotic and hypertrophic genes (RT-PCR, Western Blot) as well as the postmortal ventricular geometry were determined after four weeks. Results: No changes occurred in any parameters in the LV independent of the treatment scheme. In contrast, RV of the L and L/H group displayed a significant increase in TGFb (+94%) and collagen (+105%) expression and indicated signs of a dilated cardiomyopathy. These changes could be prevented by additional feeding of captopril (L/C). In isolated cardiomyocytes of untreated rats L-NAME treatment led to an increased ROS production (+49%) which could be blocked by preincubation with captopril. The observation that only RV were affected by this mechanism could be explained by a worsening of the Decorin/Bigycan ratio in RV only and a subsequent increase in TGFb activity. Conlusion: Increased levels of TGFb are responsible for an upregulation of collagen synthesis in RV in chronic NO deficient rats. The cardioprotective effects of captopril are mediated through a normalization of ROS production and the Decorin/Biglycan ratio independent of blood pressure reducing effects.