RENAL RESPONSES TO INTRAARTERIAL ADMINISTRATION OF NITRIC-OXIDE DONOR IN DOGS

Inhibition of nitric oxide synthesis by intra-arterial administration of nitro-L-arginine (NLA) leads to attenuation of the slope of the relation between renal arterial pressure (RAP) and sodium excretion without an alteration in renal autoregulatory efficiency. In the present study, we examined whether only the presence of nitric oxide or, alternatively, changes in nitric oxide production during changes in RAP are required for pressure natriuresis to occur. Anesthetized sodium-replete dogs (n=8) were treated with NLA (50 mug . kg-1 . min-1) to inhibit endogenous nitric oxide formation, and S-nitroso-n-acetylpenicillamine (SNAP) was infused intra-arterially at a constant rate (2 mug . kg-1 . min-1) to replenish intrarenal nitric oxide levels. Renal responses to reductions in RAP within the autoregulatory range were assessed before and during NLA infusion followed by SNAP+NLA infusion. As reported previously, NLA infusion alone increased renal vascular resistance and decreased renal blood flow, urine flow, sodium excretion, and fractional excretion of sodium, with no change in glomerular filtration rate. Autoregulatory efficiency remained intact, whereas the pressure-induced natriuretic responses were attenuated. During SNAP+NLA infusion, renal blood flow increased from 2.8+/-0.3 to 3.5+/-0.3 mL-min-1.g-1 (P<.001), without significant changes in glomerular filtration rate (0.75+/-0.07 to 0.81+/-0.05 mL . min-1 . g-1); the autoregulatory efficiency of renal blood flow and glomerular filtration rate remained intact. SNAP increased urine flow (4.8+/-1.8 to 10.0+/-2.5 muL . min-1 . g-1), sodium excretion (0.63+/-0.26 to 1.70+/-0.37 mumol . min-1 . g-1), and fractional excretion of sodium (0.55+/-0.20% to 1.38+/-0.27%). Despite the natriuresis induced by SNAP, the slope of the relation between sodium excretion and RAP remained attenuated. These data support the concept that alterations in intrarenal nitric oxide production during changes in RAP participate in the mediation of pressure natriuresis.