Influence of irbesartan and enalapril on changes of renal function associated with the established phase of l-NAME hypertension

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Abstract
Reversibility of the systemic and renal alterations induced by Nω-nitro-l-arginine-methyl ester (l-NAME) was assessed by treatment with irbesartan and enalapril (30 and 10 mg/kg per 24 h, respectively) alone or in combination. l-NAME (20 mg/kg per 24 h) was given to rats for 6 weeks and treatments were administered during the last 2 weeks. Glomerular filtration rate and renal plasma flow [GFR and RPF per g of kidney weight (KW)] were determined using the clearance technique. Arterial pressure was similarly reduced by treatments. GFR was lower in l-NAME-treated rats than in controls (552 ± 52 versus 1106 ± 78 μl/min per g KW), whereas RPF was reduced to a larger extent, thus resulting in an increase in filtration fraction. GFR was normalized by irbesartan but not enalapril or the combination (1042 ± 50, 790 ± 79 and 725 ± 38 μl/min per g KW, respectively). RPF returned to normal and filtration fraction fell markedly with the combination. All treatments reduced the lesions of preglomerular vessels and reversed l-NAME-induced albuminuria and cardiovascular hypertrophy. At a dose of 3 mg/kg per 24 h, irbesartan only reduced the lesions of the afferent arteriole. Through its effects on AT1 receptors, angiotensin II may play an important role in the maintenance of l-NAME hypertension and associated alterations. The lower GFR and filtration fraction observed with enalapril in the presence of irbesartan suggests the intervention of non-angiotensin II-mediated mechanism, and at the postglomerular level, in the effect of angiotensin-converting enzyme (ACE) inhibitors.