Renal sodium handling in experimental diabetes: role of NO

Recent studies have suggested that diabetes is a state of increasedrenal nitric oxide (NO) activity as assessed by urinary excretionof nitrites and nitrates (NO_x), and that NO synthase inhibitorsreverse the increased glomerular filtration rate (GFR) observedin experimental diabetes. In addition to being a potent vasodilatorin the renal vasculature, NO also plays a role in modulationof renal sodium excretion. To explore the role of NO in diabetes-associatedalterations in renal excretory function, renal haemodynamicand sodium handling parameters were evaluated in conscious control(C) and streptozotocin diabetic rats (D) and correlated to therenal activity of NO, as assessed by urinary excretion of itsmetabolites NO_x. To further explore this issue, the changesin renal haemodynamics and sodium handling were also assessedafter NO synthase inhibition with a non-pressor dose of L-nitro-arginine-methyl-ester(L-NAME) and after administration of the NO donor, glyceryltrinitrate (GTN). Systolic blood pressure was not differentbetween C and D rats. D rats exhibited marked hyperglycaemia(P<0.001), and increases in GFR (P<0.001), renal plasmaflow, filtration fraction, urinary sodium excretion (U_NaV, P<0.001),filtered load of sodium (FL_Na, P<0.01), and a decrease infractional reabsorption of sodium (FR_Na, P<0.0001). In contrast,total reabsorption of sodium (TR_Na) was increased in D ratscompared to C rats (P<0.0001). The urinary excretion of NOwas markedly increased in D rats (P<0.01). Regression analysesperformed in D rats revealed a close relationship between U_NaVand GFR and a weaker correlation with urinary NO_x. AlthoughFR_Na correlated only with urinary excretion of NO_x, there wasa strong relationship between TR_Na and GFR. In contrast to Drats, control rats demonstrated only a relationship betweenTR_Na and GFR and no other correlations were found, in D rats,NO inhibition with L-NAME (1 mg/kg body weight) resulted ina marked decrease in GFR and urinary NO_x associated with decreasesin FL_Na and TR_Na but did not influence FR_Na. In contrast, inC rats the post-L-NAME decrease in NO_x was not associated withsignificant changes in GFR and renal sodium handling. GTN-treatedC rats exhibited a renal vasodilatory response and an increasein natriuresis and urinary NO_x whereas no renal changes wereobserved in D rats during GTN administration. The present dataindicate that changes in renal sodium handling before and afterNO modulation in experimental diabetes are related to changesin GFR rather than to the renal activity of NO. Therefore, incontrast to the effects on renal haemodynamics, NO does notplay an important role in the altered renal sodium handlingobserved in experimental diabetes.