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

Objective Reversibility of the systemic and renal alterations induced by AP -nitro-L-arginine-methyl ester (L-NAME) was assessed by treatment with irbe sartan and enalapril (30 and 10 mg/kg per 24 h, respectively) alone or in c ombination. Design L-NAME (20 mg/kg per 24 h) was given to rats for 6 weeks and treatme nts were administered during the last 2 weeks. Glomerular filtration rate a nd renal plasma flow [GFR and RPF per g of kidney weight (KW)] were determi ned using the clearance technique. Results Arterial pressure was similarly reduced by treatments. GFR was lowe r in L-NAME-treated rats than in controls (552 +/- 52 versus 1106 +/- 78 mu l/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 bu t not enalapril or the combination (1042 +/- 50, 790 +/- 79 and 725 +/- 38 mul/min per g KW, respectively). RPF returned to normal and filtration frac tion fell markedly with the combination. All treatments reduced the lesions of preglomerular vessels and reversed L-NAME-induced albuminuria and cardi ovascular hypertrophy. At a dose of 3 mg/kg per 24 h, irbesartan only reduc ed the lesions of the afferent arteriole. Conclusions Through its effects on AT(1) 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 a ngiotensin-converting enzyme (ACE) inhibitors. (C) 2001 Lippincott Williams & Wilkins.