RENAL RESPONSES TO INTRAARTERIAL ADMINISTRATION OF NITRIC-OXIDE DONORIN DOGS

Inhibition of nitric oxide synthesis by intra-arterial administration of nitro-L-arginine (NLA) leads to attenuation of the slope of the rel ation between renal arterial pressure (RAP) and sodium excretion witho ut an alteration in renal autoregulatory efficiency. In the present st udy, we examined whether only the presence of nitric oxide or, alterna tively, changes in nitric oxide production during changes in RAP are r equired for pressure natriuresis to occur. Anesthetized sodium-replete dogs (n=8) were treated with NLA (50 mug . kg-1 . min-1) to inhibit e ndogenous 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 t o reductions in RAP within the autoregulatory range were assessed befo re 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 fractio nal excretion of sodium, with no change in glomerular filtration rate. Autoregulatory efficiency remained intact, whereas the pressure-induc ed natriuretic responses were attenuated. During SNAP+NLA infusion, re nal 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. S NAP 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%). Despit e the natriuresis induced by SNAP, the slope of the relation between s odium excretion and RAP remained attenuated. These data support the co ncept that alterations in intrarenal nitric oxide production during ch anges in RAP participate in the mediation of pressure natriuresis.