Renoprotective Effects of Captopril in Hypertension Induced by Nitric Oxide Synthase Inhibition in Experimental Nephritis

Abstract

Objective: To investigate effects of angiotensin I converting enzyme (ACE) inhibition in experimental nephritis during chronic inhibition of nitric oxide (NO) synthase. Methods: Rats with and without autoimmune Heymann nephritis 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. Urinary cGMP excretion was used as an indirect measure of NO activity. Blood pressure, urinary albumin, nitrite and nitrate levels, plasma ANP, and plasma renin activity were measured. Kidneys were examined with light microscopy and immunohistochemical methods. Results: Captopril treatment protected rats receiving L-NAME and none of the captopril-treated rats died. Mortality was greatest in the nephritis-L-NAME (57%) and L-NAME (43%) groups. Captopril normalized cGMP excretion, blood pressure, and prevented partly the appearance of albuminuria. Peritubular infiltration of mononuclear cells was clearly enhanced in the nephritis-L-NAME group (found in 80% of the rats) as compared with the nephritis (20%), L-NAME (40%), and control (0%) groups. The peritubular cell infiltration caused by L-NAME was prevented by captopril treatment. L-NAME-induced hypertension was associated with cardiac hypertrophy and this was prevented by captopril. Conclusions: NO may play an important renoprotective role in disease progression of chronic membranous glomerulonephritis. Captopril prevents L-NAME-induced hypertension, improves survival, and ameliorates renal damage in this type of nephritis. Dysfunction of renal NO pathways may be an important factor causing progressive renal damage in chronic nephritis. Our results suggest that the dysfunctional renal NO system may be beneficially activated by ACE inhibitors.