Renoprotective effects of captopril in hypertension induced by nitric oxide synthase inhibition in experimental nephritis

Objective: To investigate effects of angiotensin I converting enzyme (ACE) inhibition in experimental nephritis during chronic inhibition of nitric ox ide (NO) synthase. Methods: Rats with and without autoimmune Heymann nephri tis were treated with a NO synthase inhibitor L-NAME (50 mg/100 ml) and/or an ACE inhibitor captopril (20 mg/100 ml) in drinking water for 12 weeks. U rinary cGMP excretion was used as an indirect measure of NO activity. Blood pressure, urinary albumin, nitrite and nitrate revels, plasma ANP, and pla sma renin activity were measured. Kidneys were examined with light microsco py and immunohistochemical methods. Results: Captopril treatment protected rats receiving L-NAME and none of the captopril-treated rats died. Mortalit y was greatest in the nephritis-L-NAME (57%) and L-NAME (43%) groups. Capto pril normalized cGMP excretion, blood pressure, and prevented partly the ap pearance of albuminuria. Peritubular infiltration of mononuclear cells was clearly enhanced in the nephritis-L-NAME group (found in 80% of the rats) a s compared with the nephritis (20%), L-NAME (40%), and control (0%) groups. The peritubular cell infiltration caused by L-NAME was prevented by captop ril treatment. L-NAME-induced hypertension was associated with cardiac hype rtrophy and this was prevented by captopril. Conclusions: NO may play an im portant renoprotective role in disease progression of chronic membranous gl omerulonephritis. Captopril prevents L-NAME-induced hypertension, improves survival, and ameliorates renal damage in this type of nephritis. Dysfuncti on of renal NO pathways may be an important factor causing progressive rena l damage in chronic nephritis. Our results suggest that the dysfunctional r enal NO system may be beneficially activated by ACE inhibitors.