title: The intrarenal generation of angiotensin II is required for experimental hypertension.
abstract: Hypertension is a major risk factor for cardiovascular disease. While the cause of hypertension is multifactorial, renal dysregulation of salt and water excretion is a major factor. All components of the renin-angiotensin system are produced locally in the kidney, suggesting that intrarenal generation of angiotensin II plays a key role in blood pressure regulation. Here, we show that two mouse models lacking renal angiotensin converting enzyme (ACE) are protected against angiotensin II and l-NAME induced hypertension. In response to hypertensive stimuli, mice lacking renal ACE do not produce renal angiotensin II. These studies indicate that the intrarenal renin-angiotensin system works as an entity separate from systemic angiotensin II generation. Renal ACE appears necessary for experimental hypertension.
authors.affiliation: Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Jorge F
authors.initials: JF
authors.lastname: Giani
authors.affiliation: Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Kandarp H
authors.initials: KH
authors.lastname: Shah
authors.affiliation: Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Zakir
authors.initials: Z
authors.lastname: Khan
authors.affiliation: Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Ellen A
authors.initials: EA
authors.lastname: Bernstein
authors.affiliation: Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Xiao Z
authors.initials: XZ
authors.lastname: Shen
authors.affiliation: Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Alicia A
authors.initials: AA
authors.lastname: McDonough
authors.affiliation: Pfizer, DSRD CoE, 274 Eastern Point Road, MS 8274-1245, Groton, CT 06340, USA.
authors.forename: Romer A
authors.initials: RA
authors.lastname: Gonzalez-Villalobos
authors.affiliation: Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Electronic address: kenneth.bernstein@cshs.org.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Bernstein
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology
chemical_list: D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A