NITRIC OXIDE-INHIBITORY EFFECT OF AMINOGUANIDINE ON RENAL-FUNCTION INRATS

Inhibition of nitric oxide (NO) synthesis by structural analogues of L -arginine reduces glomerular filtration, renal blood flow, sodium excr etion, and urine output. N-G-nitro L-arginine methyl ester (L-NAME) in hibits constitutive and inducible isoforms of NO synthase, while amino guanidine (AG) selectively inhibits inducible isoforms of NO synthase. We assessed the NO-inhibitory activity of AC; on renal function. Rats were treated with aminoguanidine 50 mg/kg daily for 2 months, followe d by L-NAME (25 mg/kg/day) for 1 week to inhibit all NO synthase isofo rms. After treatment with L-NAME, we performed baseline renal function measurements, then infused L-arginine (2.5 mg/100 g BW x min) to reve rse NO inhibition and assessed whether AG exerted NO-inhibitory activi ty independently of L-NAME. Prior to L-arginine infusion, AG-treated r ats did not differ from controls with respect to body weight, kidney w eight, systolic blood pressure, urine flow rate: urinary protein or al bumin excretion, or urinary excretion of NO metabolites. After L-argin ine infusion, all animals showed a 10-15% decrease in mean arterial bl ood pressure. L-Arginine-induced increases in urine flow, inulin clear ance, PAH clearance, sodium excretion, and NO metabolite excretion wer e blunted in aminoguanidine-treated animals. To assess long-term effec ts of aminoguanidine, rats were treated for 12 months. Urinary excreti on of NO metabolites was lower than controls. Inulin clearance was hig her than controls. Aminoguanidine blunts the effect of L-ariginine on renal hemodynamics independently of the nitric oxide synthase inhibito r, L-NAME. However, the use of aminoguanidine for 12 months in rats di d not adversely affect renal function.