Experimental evidence has now been amassed to indicate that inhibition of nitric oxide (NO) synthase reduces total or regional renal blood flow by approximately 25 to 30% and markedly increases the renal vascular resistance, demonstrating that basal release of NO helps to maintain the relatively low vascular resistance that is characteristic for the kidney. It has been demonstrated that intraarterial administration of NO synthase inhibitors causes marked reductions in sodium excretion without changes in filtered load and suppressed the arterial pressure-induced natriuretic responses in the kidney. We also demonstrated that a constant rate infusion of a NO donor in dogs pretreated with a NOS inhibitor resulted in increases in sodium excretion but failed to restore the slope of the relation between arterial pressure and sodium excretion, suggesting that an alteration in intrarenal NO production rate during changes in arterial pressure is involved in the mediation of pressure natriuresis. Further experiments in dogs performed in our laboratory have confirmed that there is a direct relationship between changes in arterial pressure and intrarenal NO activity measured using NO-sensitive microelectrodes in the renal tissue. These arterial pressure-induced changes in intrarenal NO activity were seen positively correlated with the changes in urinary excretion rates of sodium. Collectively, these data suggest that acute changes in arterial pressure alter intrarenal NO production, which inhibits tubular sodium reabsorption to manifest the phenomenon of pressure natriuresis.