ABNORMAL RENAL HEMODYNAMIC-RESPONSE TO REDUCED RENAL PERFUSION-PRESSURE IN DIABETIC RATS - ROLE OF NO

Diabetic rats manifest abnormal renal hemodynamic responses, with pers istent renal vasodilation at reduced renal perfusion pressures. We hyp othesized that in diabetes, renal hemodynamics are modulated by increa sed activity of the endogenous vasodilator, NO. In anesthetized Munich -Wistar rats, after 6 wk of streptozotocin-induced, insulin-treated di abetes, and in age-matched, nondiabetic littermates (n = 7-8), basal, renal hemodynamics and responses to graded reductions in renal perfusi on pressure were determined before and after intrarenal arterial infus ion of the NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester ( L-NAME). An identical protocol was followed in a second cohort of rats pretreated with indomethacin (4 mg/kg iv). Diabetic rats demonstrated hyperglycemia, renal enlargement, hyperfiltration, and increased urin ary excretion of the stable NO metabolites, NO2 and NO3. L-NAME elimin ated basal hyperfiltration in diabetic rats, and L-NAME, but not indom ethacin, also eliminated persistent renal vasodilation at reduced rena l perfusion pressure. We conclude that in a rat model of diabetes, inc reased endogenous NO activity may play a role in basal hyperfiltration and in the persistent renal vasodilatation manifested at reduced rena l perfusion pressures.