Angiotensin type 1 receptor antagonism and ACE inhibition produce similar renoprotection in N-omega-nitro-L-arginine methyl ester/spontaneously hypertensive rats

This study was conducted to determine potentially differential effects betw een an angiotensin II type 1 (AT(1)) receptor antagonist and an ACE inhibit or on systemic, renal, and glomerular hemodynamics and pathological changes in spontaneously hypertensive rats (SHR) with N-omega-nitro-L-arginine met hyl ester (L-NAME)-exacerbated nephrosclerosis. The hemodynamic, renal micr opuncture, and pathological studies were performed in 9 groups of 17-week-o ld male SHR treated as follows: group 1, controls (n=16); group 2, candesar tan (10 mg/kg per day for 3 weeks) (n=7); group 3, enalapril (30 mg/kg per day for 3 weeks) (n=8); group 4, candesartan (5 mg/kg per day) plus enalapr il (15 mg/kg per day for 3 weeks) (n=9); group 5, L-NAME (50 mg/L in drinki ng water for 3 weeks) (n=17); group 6, L-NAME (50 mg/L) plus candesartan (1 0 mg/kg per day for 3 weeks) (n=7); group 7, L-NAME (50 mg/L) for 3 weeks f ollowed by candesartan (10 mg/kg per day) for another 3 weeks (n=8); group 8, L-NAME (50 mg/L) plus enalapril (30 mg/kg per day for 3 weeks) (n=7); an d group 9, L-NAME (50 mg/L) plus enalapril (30 mg/kg per day) and the brady kinin antagonist icatibant (500 mug/kg SC per day via osmotic minipump for 3 weeks) (n=7). Both candesartan and enalapril similarly reduced mean arter ial pressure and total peripheral resistance index. These changes were asso ciated with significant decreases in afferent and efferent glomerular arter iolar resistances as well as glomerular capillary pressure. Histopathologic ally, the glomerular and arterial injury scores were decreased significantl y, and left ventricular and aortic masses also were diminished significantl y in all treated groups. L-NAME-induced urinary protein excretion was preve nted by both candesartan and enalapril. Thus, both AT(1) receptor and ACE i nhibition prevented and reversed the pathophysiological alterations of L-NA ME-exacerbated nephrosclerosis in SHR. Itatibant only blunted the antihyper tensive effects of enalapril but did not attenuate the beneficial effects o f ACE inhibition on the L-NAME-induced nephrosclerosis. Thus, the AT(1) rec eptor antagonism and ACE inhibition have similar renal preventive effects, which most likely were achieved through reduction in the effects of angiote nsin II, and ACE inhibition of bradykinin degradation demonstrated little e vidence of renoprotection.