title: Renal collecting duct NOS1 maintains fluid-electrolyte homeostasis and blood pressure.
abstract: Nitric oxide is a pronatriuretic and prodiuretic factor. The highest renal NO synthase (NOS) activity is found in the inner medullary collecting duct. The collecting duct (CD) is the site of daily fine-tune regulation of sodium balance, and led us to hypothesize that a CD-specific deletion of NOS1 would result in an impaired ability to excrete a sodium load leading to a salt-sensitive blood pressure phenotype. We bred AQP2-CRE mice with NOS1 floxed mice to produce flox control and CD-specific NOS1 knockout (CDNOS1KO) littermates. CDs from CDNOS1KO mice produced 75% less nitrite, and urinary nitrite+nitrate (NOx) excretion was significantly blunted in the knockout genotype. When challenged with high dietary sodium, CDNOS1KO mice showed significantly reduced urine output, sodium, chloride, and NOx excretion, and increased mean arterial pressure relative to flox control mice. In humans, urinary NOx is a newly identified biomarker for the progression of hypertension. These findings reveal that NOS1 in the CD is critical in the regulation of fluid-electrolyte balance, and this new genetic model of CD NOS1 gene deletion will be a valuable tool to study salt-dependent blood pressure mechanisms.
authors.affiliation: Section of Experimental Medicine, Department of Medicine, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Hyndman
authors.forename: Erika I
authors.initials: EI
authors.lastname: Boesen
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Mansoura University, Egypt
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Elmarakby
authors.forename: Michael W
authors.initials: MW
authors.lastname: Brands
authors.forename: Paul
authors.initials: P
authors.lastname: Huang
authors.forename: Donald E
authors.initials: DE
authors.lastname: Kohan
authors.forename: David M
authors.initials: DM
authors.lastname: Pollock
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Pollock
mesh_terms: D000818:Animals; D001794:Blood Pressure; D015153:Blotting, Western; D004247:DNA / Q000235:genetics; D004195:Disease Models, Animal; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006706:Homeostasis / Q000502:physiology*; D006973:Hypertension / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D052248:Nitric Oxide Synthase Type I / Q000096:biosynthesis* / Q000235:genetics; D010641:Phenotype; D012964:Sodium / Q000378:metabolism; D012982:Sodium, Dietary / Q000633:toxicity; D014882:Water-Electrolyte Balance / Q000502:physiology
chemical_list: D012982:Sodium, Dietary; D004247:DNA; D012964:Sodium; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse
keywords: NOS1; blood pressure; collecting duct; salt-sensitivity; sodium excretion