NITRIC-OXIDE IN THE MEDIATION OF PRESSURE NATRIURESIS

1. Recent studies have indicated that nitric oxide (NO) production in the kidney contributes to the regulation of renal haemodynamics and ex cretory function, Inhibition of nitric oxide synthase (NOS) reduces re nal blood flow by approximately 25% and markedly reduces sodium excret ion without reductions in filtered load, In particular, inhibition of NO synthesis markedly suppresses the slope of the arterial pressure-me diated response in sodium excretion, 2. Further studies have shown tha t constant intrarenal infusion of a NO donor in dogs treated with a NO S inhibitor produced diuretic and natriuretic responses but failed to restore the slope of the pressure-induced natriuretic response. These data indicate that an alteration in intrarenal NO activity, rather tha n the simple presence of NO during changes in arterial pressure is req uired for full expression of pressure natriuretic responses, 3. In sup port of the hypothesis that NO is involved in the mediation of pressur e natriuresis, we also recently demonstrated a direct relationship bet ween changes in arterial pressure and urinary excretion rate of sodium as well as nitrate and nitrite (a marker for endogenous NO activity) in the presence of efficient autoregulation of cortical and medullary blood flow. 4. The direct inhibitory actions of NO on tubular sodium r eabsorption have also been observed in cultured tubular cells as well as isolated, perfused cortical collecting duct segments, 5. Thus, the collective data suggest that acute changes in arterial pressure induce changes in intrarenal NO production, which may directly alter tubular reabsorptive function to manifest the phenomenon of pressure natriure sis.