NO produced by endothelial NO synthase (eNOS) promotes diuresis and natriuresis

Abstract

Vascular NO reduces blood pressure (BP) by decreasing peripheral resistance. Renal NO reduces BP by increasing glomerular filtration and inhibiting water and Na absorption along the nephron. Renal nNOS plays a major role in water and Na excretion, but iNOS's is minor. The role that eNOS plays is unclear. We hypothesized that NO produced by eNOS promotes excretion of water and Na, and this is primarily a renal effect. To test our hypothesis we gave conscious wild‐type (WT) and eNOS knockout (−/−) mice a volume load and measured urinary volume (UV), Na excretion (UVNa) and excretion of osmoles (UVOsm) over 3 hrs. We also measured BP and plasma renin concentration (PRC). To give the volume load we trained mice to drink a large volume of water in 3 hrs while in metabolic cages. On the day of the experiment water was replaced with 1% sucrose, and mice only had access to it for 1 hr. Intake was similar in both groups. Over 3 hrs WT excreted 62 ± 10 % of intake, but eNOS −/− excreted only 42 ± 5 % (p ≤ 0.05). Na excretion was 49.3 ± 7.0 in WT vs. 37.8 ± 6.4 umoles/3 hrs in eNOS −/− (p ≤ 0.05). UVOsm was also decreased by 25% in eNOS −/− (p ≤ 0.05). Pressure natriuresis was not the cause because BP in eNOS −/− was 118 ± 3 compared to 110 ± 2 mm Hg in WT (p ≤ 0.05). PRC was similar in both strains. We conclude that NO produced by eNOS promotes water and Na excretion. This is likely due to renal eNOS because the effects of NO on the systemic vasculature promote Na and water retention.