Collecting duct-specific knockout of nitric oxide synthase 3 impairs water
excretion in a sex-dependent manner.
Authors Gao Y, Stuart D, Pollock JS, Takahishi T, Kohan DE
Submitted By Submitted Externally on 6/5/2017
Status Published
Journal American journal of physiology. Renal physiology
Year 2016
Date Published 11/1/2016
Volume : Pages 311 : F1074 - F1083
PubMed Reference 27707708
Abstract Nitric oxide (NO) inhibits collecting duct (CD) Na(+) and water reabsorption.
Mice with CD-specific knockout (KO) of NO synthase 1 (NOS1) have salt-sensitive
hypertension. In contrast, the role of NOS3 in CD salt and water reabsorption is
unknown. Mice with CD NOS3 KO were generated with loxP-flanked exons 9-12
(encodes the calmodulin binding site) of the NOS3 gene and the aquaporin-2
promoter-Cre transgene. There were no differences between control and CD NOS3 KO
mice, irrespective of sex, in food intake, water intake, urine volume, urinary
Na(+) or K(+) excretion, plasma renin concentration, blood pressure, or pulse
during 7 days of normal (0.3%), high (3.17%), or low (0.03%) Na(+) intake. Blood
pressure was similar between genotypes during DOCA-high salt. CD NOS3 KO did not
alter urine volume or urine osmolality after water deprivation. In contrast, CD
NOS3 KO male, but not female, mice had lower urine volume and higher urine
osmolality over the course of 7 days of water loading compared with control
mice. Male, but not female, CD NOS3 KO mice had reduced urinary nitrite+nitrate
excretion compared with controls after 7 days of water loading. Urine AVP and
AVP-stimulated cAMP accumulation in isolated inner medullary CD were similar
between genotypes. Western analysis did not reveal a significant effect of CD
NOS3 KO on renal aquaporin expression. In summary, these data suggest that CD
NOS3 may be involved in the diuretic response to a water load in a sex-specific
manner; the mechanism of this effect remains to be determined.

Complications