title: Role of Angiotensin II type 1 receptor on renal NAD(P)H oxidase, oxidative stress and inflammation in nitric oxide inhibition induced-hypertension.
abstract: OBJECTIVE
  Activation of the renin-angiotensin system (RAS), renal oxidative stress and inflammation are constantly present in experimental hypertension. Nitric oxide (NO) inhibition with N(w)-nitro-L-arginine methyl ester (L-NAME) has previously been reported to produce hypertension, increased expression of Angiotensin II (Ang II) and renal dysfunction. The use of Losartan, an Ang II type 1 receptor (AT1R) antagonist has proven to be effective reducing hypertension and renal damage; however, the mechanism by which AT1R blockade reduced kidney injury and normalizes blood pressure in this experimental model is still complete unknown. The current study was designed to test the hypothesis that AT1R activation promotes renal NAD(P)H oxidase up-regulation, oxidative stress and cytokine production during L-NAME induced-hypertension.
  
  
  METHODS
  Male Sprague-Dawley rats were distributed in three groups: L-NAME, receiving 70 mg/100ml of L-NAME, L-NAME+Los, receiving 70 mg/100ml of L-NAME and 40 mg/kg/day of Losartan; and Controls, receiving water instead of L-NAME or L-NAME and Losartan.
  
  
  RESULTS
  After two weeks, L-NAME induced high blood pressure, renal overexpression of AT1R, NAD(P)H oxidase sub-units gp91, p22 and p47, increased levels of oxidative stress, interleukin-6 (IL-6) and interleukin-17 (IL-17). Also, we found increased renal accumulation of lymphocytes and macrophages. Losartan treatment abolished the renal expression of gp91, p22, p47, oxidative stress and reduced NF-κB activation and IL-6 expression.
  
  
  CONCLUSIONS
  These findings indicate that NO induced-hypertension is associated with up-regulation of NADPH oxidase, oxidative stress production and overexpression of key inflammatory mediators. These events are associated with up-regulation of AT1R, as evidenced by their reversal with AT1R blocker treatment.
authors.affiliation: Centro de Medicina y Cirugía Experimental, Universidad del Zulia, Venezuela.
authors.forename: J
authors.initials: J
authors.lastname: Rincón
authors.affiliation: Centro de Investigaciones Biomédicas, IVIC-Zulia, Venezuela.
authors.forename: D
authors.initials: D
authors.lastname: Correia
authors.affiliation: Instituto de Investigaciones Clínicas "Dr. Américo Negrette", Universidad del Zulia, Venezuela.
authors.forename: J L
authors.initials: JL
authors.lastname: Arcaya
authors.affiliation: Philosophisch-Naturwissenschaftliche Fakultät, Universität Basel, Yong Loo Lin School of Medicine, National University of, Singapore.
authors.forename: E
authors.initials: E
authors.lastname: Finol
authors.affiliation: Instituto de Investigaciones Clínicas "Dr. Américo Negrette", Universidad del Zulia, Venezuela.
authors.forename: A
authors.initials: A
authors.lastname: Fernández
authors.affiliation: Centro de Investigaciones Biomédicas, IVIC-Zulia, Venezuela.
authors.forename: M
authors.initials: M
authors.lastname: Pérez
authors.affiliation: Centro de Investigaciones Biomédicas, IVIC-Zulia, Venezuela.
authors.forename: K
authors.initials: K
authors.lastname: Yaguas
authors.affiliation: Centro de Investigaciones Biomédicas, IVIC-Zulia, Venezuela.
authors.forename: E
authors.initials: E
authors.lastname: Talavera
authors.affiliation: Escuela de Medicina, Universidad del Zulia, Venezuela.
authors.forename: M
authors.initials: M
authors.lastname: Chávez
authors.affiliation: Center for Translational Medicine and Jane and Leonard Korman Lung Center, Thomas Jefferson University, Philadelphia, USA.
authors.forename: R
authors.initials: R
authors.lastname: Summer
authors.affiliation: Center for Translational Medicine and Jane and Leonard Korman Lung Center, Thomas Jefferson University, Philadelphia, USA. Electronic address: frromero_vasquez@hotmail.com.
authors.forename: F
authors.initials: F
authors.lastname: Romero
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology*; D020381:Interleukin-17 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D000074663:NADPH Oxidase 4; D016328:NF-kappa B / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D020381:Interleukin-17; D015850:Interleukin-6; D016328:NF-kappa B; D044140:Receptor, Angiotensin, Type 1; D009569:Nitric Oxide; D009247:NADH, NADPH Oxidoreductases; D000074663:NADPH Oxidase 4; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester
keywords: AT1R; Hypertension; IL-17; IL-6; L-NAME; NADPH