title: Cytosolic Phospholipase A2α Is Essential for Renal Dysfunction and End-Organ Damage Associated With Angiotensin II-Induced Hypertension.
abstract: BACKGROUND
  The kidney plays an important role in regulating blood pressure (BP). cPLA2α in the kidney is activated by various agents including angiotensin II (Ang II) and selectively releases arachidonic acid (AA) from tissue lipids, generating pro- and antihypertensive eicosanoids. Since activation of cPLA2α is the rate-limiting step in AA release, this study was conducted to determine its contribution to renal dysfunction and end-organ damage associated with Ang II-induced hypertension.
  
  
  METHODS
  cPLA2α(+/+) and cPLA2α(-/-) mice were infused with Ang II (700 ng/ kg/min) or its vehicle for 13 days. Mice were placed in metabolic cages to monitor their food and water intake, and urine was collected and its volume was measured. Doppler imaging was performed to assess renal hemodynamics. On the 13th day of Ang II infusion, mice were sacrificed and their tissues and blood collected for further analysis.
  
  
  RESULTS
  Ang II increased renal vascular resistance, water intake, and urine output and Na(+) excretion, decreased urine osmolality, and produced proteinuria in cPLA2α(+/+) mice. Ang II also caused accumulation of F4/80(+) macrophages and CD3(+) T cells and renal fibrosis, and increased oxidative stress in the kidneys of cPLA2α(+/+) mice. All these effects of Ang II were minimized in cPLA2α(-/-) mice.
  
  
  CONCLUSIONS
  cPLA2α contributes to renal dysfunction, inflammation, and end-organ damage, most likely via the action of pro-hypertensive eicosanoids and increased oxidative stress associated with Ang II-induced hypertension. Thus, cPLA2α could serve as a potential therapeutic target for treating renal dysfunction and end-organ damage in hypertension.
authors.affiliation: Department of Pharmacology, College of Medicine, The University of Tennessee Health Science Center, Memphis, Tennessee, USA;
authors.forename: Nayaab S
authors.initials: NS
authors.lastname: Khan
authors.affiliation: Department of Pharmacology, College of Medicine, The University of Tennessee Health Science Center, Memphis, Tennessee, USA;
authors.forename: Chi Young
authors.initials: CY
authors.lastname: Song
authors.affiliation: Department of Pharmacology, College of Medicine, The University of Tennessee Health Science Center, Memphis, Tennessee, USA;
authors.forename: Shyamala
authors.initials: S
authors.lastname: Thirunavukkarasu
authors.affiliation: Department of Pharmacology, College of Medicine, The University of Tennessee Health Science Center, Memphis, Tennessee, USA;
authors.forename: Xiao R
authors.initials: XR
authors.lastname: Fang
authors.affiliation: Renal Division, Department of Medicine, Brigham and Women's Hospital Boston, Harvard Medical School, Harvard Institute of Medicine, Boston, Massachusetts, USA.
authors.forename: Joseph V
authors.initials: JV
authors.lastname: Bonventre
authors.affiliation: Department of Pharmacology, College of Medicine, The University of Tennessee Health Science Center, Memphis, Tennessee, USA; kmalik@uthsc.edu.
authors.forename: Kafait U
authors.initials: KU
authors.lastname: Malik
mesh_terms: D000804:Angiotensin II; D000818:Animals; D016232:Endothelins / Q000097:blood; D005355:Fibrosis; D054513:Group IV Phospholipases A2 / Q000235:genetics / Q000378:metabolism*; D006973:Hypertension / Q000150:complications / Q000201:enzymology*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology; D008297:Male; D051379:Mice; D012079:Renal Circulation; D014655:Vascular Resistance
chemical_list: D016232:Endothelins; D000804:Angiotensin II; D054513:Group IV Phospholipases A2
keywords: angiotensin II; blood pressure; cPLA2α−/− mice; fibrosis; hypertension; inflammation; oxidative stress; proteinuria; renal hemodynamics.