title: Nitric oxide and the A and B of endothelin of sodium homeostasis.
abstract: OBJECTIVE
  In recent years, renal collecting duct-specific endothelin-1 (ET1), endothelin A (ETA) and endothelin B (ETB) receptors as well as nitric oxide synthase 1 (NOS1) knockout mice have been developed with subsequent identification for an integral role in regulation of sodium water homeostasis and ultimately blood pressure. The focus of this review is to integrate these models and to propose a scheme for the control of sodium excretion by the collecting duct and the endothelin/ETB/NOS system.
  
  
  RESULTS
  NOS1 splice variants are expressed in the kidney, especially in the collecting duct. Mice express predominantly NOS1β in the medulla, with NOS1α and NOS1β in the cortex, whereas rats express NOS1α and NOS1β in both the cortex and medulla. Novel transcription of collecting duct ET1 mediated by epithelial sodium channels, mitochondrial Na/Ca exchangers and glucocorticoids has been determined. ET1 via the ETB receptor increases nitric oxide production in both rat and mouse collecting ducts, suggesting that NOS1β is linked to ET1-dependent NOS activation in the kidney. As well, genetic deletion of NOS1 splice variants in the collecting duct results in a salt-sensitive hypertensive phenotype in mice, much like the collecting duct ET1 and collecting duct ETB knockout mice.
  
  
  CONCLUSIONS
  In the collecting duct, the ET1/nitric oxide pathways are intimately linked, and deletion of collecting duct ET1, ETB receptor or NOS1β results in a salt-sensitive phenotype, which is at least partially dependent on dysregulation of sodium and water reabsorption.
authors.affiliation: Department of Medicine, Section of Experimental Medicine, Georgia Health Sciences University, Augusta, Georgia 30912, USA.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Hyndman
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Pollock
mesh_terms: D000818:Animals; D019332:Endothelin-1 / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D023421:Models, Animal; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism*; D014867:Water / Q000378:metabolism
chemical_list: D019332:Endothelin-1; D014867:Water; D012964:Sodium; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse