Nitric oxide produced by endothelial nitric oxide synthase promotes diuresis

Perez-Rojas JM, Kassem KM, Beierwaltes WH, Garvin JL, Herrera M. Nitric oxide produced by endothelial nitric oxide synthase promotes diuresis. Am J Physiol Regul Integr Comp Physiol 298: R1050-R1055, 2010. First published February 10, 2010; doi: 10.1152/ajpregu.00181.2009.-Extracellular fluid volume is highly regulated, at least in part, by peripheral resistance and renal function. Nitric oxide (NO) produced by NO synthase type 3 (NOS 3) in the nonrenal vasculature may promote fluid retention by reducing systemic vascular resistance and arterial pressure. In contrast, NO produced by renal NOS 3 promotes water excretion by reducing renal vascular resistance, increasing glomerular filtration, and inhibiting reabsorption along the nephron. Thus, the net effect of NO from NOS 3 on urinary volume (UV) is unclear. We hypothesized that NO produced by NOS 3 promotes water excretion primarily due to renal tubular effects. We gave conscious wild-type and NOS 3 -/- mice an acute volume load and measured UV, blood pressure, plasma renin concentration (PRC), Na+, vasopressin, and urinary Na+ and creatinine concentrations. To give the acute volume load, we trained mice to drink a large volume of water while in metabolic cages. On the day of the experiment, water was replaced with 1% sucrose, and mice had access to it for 1 h. Volume intake was similar in both groups. Over 3 h, wild-type mice excreted 62 +/- 10% of the volume load, but NOS 3 -/- excreted only 42 +/- 5% (P < 0.05). Blood pressure in NOS 3 -/- was 118 +/- 3 compared with 110 +/- 2 mmHg in wild-type mice (P < 0.05), but it did not change following volume load in either strain. PRC, vasopressin, and glomerular filtration rate were similar between groups. Urinary Na+ excretion was 49.3 +/- 7.0 in wild-type vs. 37.8 +/- 6.4 mu mol/3 h in NOS 3-/- mice (P < 0.05). Bumetanide administration eliminated the difference in volume excretion between wild-type and NOS 3-/- mice. We conclude that 1) NO produced by NOS 3 promotes water and Na+ excretion and 2) the renal epithelial actions of NO produced by NOS 3 supersede the systemic and renal vascular actions.