RENAL EFFECTS OF ACUTE AND CHRONIC NITRIC-OXIDE INHIBITION IN EXPERIMENTAL DIABETES

We investigated whether nitric oxide (NO) contributes to glomerular hy perfiltration in experimental diabetes. Thirty-five adult male Munich- Wistar streptozocin-diabetic rats and 39 nondiabetic controls were dis tributed among 4 groups: C, normal controls; C + L-NAME, controls rece iving the NO inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), 40 mg/dl in drinking water; DM, diabetic rats; DM + L-NAME, diabetic rats receiving L-NAME, 15 mg/dl in drinking water. After 1 month of tr eatment, the DM + L-NAME group exhibited renal vasoconstriction and la cked hyperfiltration. Acute administration of L-NAME, 2.5 mg/kg, depre ssed the glomerular filtration rate and promoted renal vasoconstrictio n to a much greater extent in the DM than in the C group. Acute admini stration of endothelin 1 (600 ng/kg, bolus) or angiotensin II (25 mu g /kg/min, continuous infusion) exerted similar hemodynamic effects in t he C and DM groups, suggesting that the enhanced response of DM to L-N AME reflected specific sensitivity to NO inhibition. Urinary excretion of nitrites and nitrates was fourfold higher in DM compared to C. The se results support the notion that augmented NO production may contrib ute to renal hyperfiltration and hyperperfusion in diabetes.