Nitric oxide produced by endothelial nitric oxide synthase promotes diuresis.
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 mumol/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.
Division of Hypertension and Vascular Research, Henry Ford Hospital, Detroit, MI 48202, USA.
Jazmin M
JM
Perez-Rojas
Kamal M
KM
Kassem
William H
WH
Beierwaltes
Jeffrey L
JL
Garvin
Marcela
M
Herrera
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002034:Bumetanide / Q000494:pharmacology; D003404:Creatinine / Q000097:blood / Q000652:urine; D004231:Diuresis / Q000187:drug effects; D004232:Diuretics / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology*; D052250:Nitric Oxide Synthase Type III / Q000172:deficiency / Q000378:metabolism*; D012083:Renin / Q000097:blood; D012964:Sodium / Q000097:blood / Q000652:urine
D004232:Diuretics; D002034:Bumetanide; D009569:Nitric Oxide; D012964:Sodium; D003404:Creatinine; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D012083:Renin