title: Endothelin-1 and the kidney: new perspectives and recent findings.
abstract: OBJECTIVE
  The role of endothelin-1 (ET-1) in the kidney has been under study for many years; however, the complex mechanisms by which endothelin controls the physiology/pathophysiology of this organ are not fully resolved. This review aims to summarize recent findings in the field, especially regarding glomerular and tubular damage, Na/water homeostasis and sex differences in ET-1 function.
  
  
  RESULTS
  Podocytes have been recently identified as a target of ET-1 in the glomerular filtration barrier via ETA receptor activation. Activation of the ETA receptor by ET-1 leads to renal tubular damage by promoting endoplasmic reticulum stress and apoptosis in these cells. In addition, high flow rates in the nephron in response to high salt intake induce ET-1 production by the collecting ducts and promote nitric oxide-dependent natriuresis through epithelial sodium channel inhibition. Recent evidence also indicates that sex hormones regulate the renal ET-1 system differently in men and women, with estrogen suppressing renal ET-1 production and testosterone upregulating that production.
  
  
  CONCLUSIONS
  Based on the reports reviewed in here, targeting of the renal endothelin system is a possible therapeutic approach against the development of glomerular injury. More animal and clinical studies are needed to better understand the dimorphic control of this system by sex hormones.
authors.affiliation: Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Carmen
authors.initials: C
authors.lastname: De Miguel
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Speed
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Kasztan
authors.forename: Eman Y
authors.initials: EY
authors.lastname: Gohar
authors.forename: David M
authors.initials: DM
authors.lastname: Pollock
mesh_terms: D000818:Animals; D059865:Endoplasmic Reticulum Stress; D065128:Endothelin Receptor Antagonists / Q000627:therapeutic use; D019332:Endothelin-1 / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D007668:Kidney / Q000502:physiology*; D007674:Kidney Diseases / Q000209:etiology; D050199:Podocytes / Q000502:physiology; D012727:Sex Characteristics; D012964:Sodium / Q000378:metabolism
chemical_list: D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D012964:Sodium