Role of nitric oxide in the mediation of pressure natriuresis.

Recent studies have indicated that nitric oxide (NO) production by renal endothelial and other cells contributes importantly to the control of renal hemodynamics and sodium excretion. Blockade of NO production by arterial infusion of L-arginine analogues that prevent formation of NO, such as nitro-L-arginine (NLA), suggest that to of the basal renal blood flow is NO dependent. NLA administration in dogs also leads to decreases in urine flow and sodium excretion by enhancing fractional reabsorption rate. Although NLA reduces blood flow, the autoregulatory mechanism for RBF and GFR remains intact. However, NLA markedly suppresses the slope of the pressure natriuresis relationship. To determine if NO mediates pressure natriuresis or if it only requires the presence of NO to be manifested, an NO donor (S-nitroso-n-acetylpenicillamine) was infused intrarenally. RBF and sodium excretion were restored towards normal values; however, the ability of Na excretion to respond to changes in arterial pressure remained suppressed. Further studies demonstrated a positive relationship between urinary nitrate (NO−3)/nitrite (NO−2) excretion rates (metabolites of NO) and RAP (n = 9). These data are consistent with the hypothesis that increases in intrarenal NO production rate during increases in RAP, probably due to increases in shear stress, serve as an important mediator of pressure natriuresis by influencing tubular transport.