title: Renal angiotensin-converting enzyme is essential for the hypertension induced by nitric oxide synthesis inhibition.
abstract: The kidney is an important source of angiotensin-converting enzyme (ACE) in many species, including humans. However, the specific effects of local ACE on renal function and, by extension, BP control are not completely understood. We previously showed that mice lacking renal ACE, are resistant to the hypertension induced by angiotensin II infusion. Here, we examined the responses of these mice to the low-systemic angiotensin II hypertensive model of nitric oxide synthesis inhibition with L-NAME. In contrast to wild-type mice, mice without renal ACE did not develop hypertension, had lower renal angiotensin II levels, and enhanced natriuresis in response to L-NAME. During L-NAME treatment, the absence of renal ACE was associated with blunted GFR responses; greater reductions in abundance of proximal tubule Na(+)/H(+) exchanger 3, Na(+)/Pi co-transporter 2, phosphorylated Na(+)/K(+)/Cl(-) cotransporter, and phosphorylated Na(+)/Cl(-) cotransporter; and greater reductions in abundance and processing of the γ isoform of the epithelial Na(+) channel. In summary, the presence of ACE in renal tissue facilitates angiotensin II accumulation, GFR reductions, and changes in the expression levels and post-translational modification of sodium transporters that are obligatory for sodium retention and hypertension in response to nitric oxide synthesis inhibition.
authors.affiliation: Departments of Biomedical Sciences and Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California;
authors.forename: Jorge F
authors.initials: JF
authors.lastname: Giani
authors.affiliation: Departments of Biomedical Sciences and Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California;
authors.forename: Tea
authors.initials: T
authors.lastname: Janjulia
authors.affiliation: Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, California;
authors.forename: Nikhil
authors.initials: N
authors.lastname: Kamat
authors.affiliation: Department of Physiology and Hypertension and Renal Center of Excellence, Tulane University, New Orleans, Louisiana;
authors.forename: Dale M
authors.initials: DM
authors.lastname: Seth
authors.affiliation: Departments of Biomedical Sciences and Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California;
authors.forename: Wendell-Lamar B
authors.initials: WL
authors.lastname: Blackwell
authors.affiliation: Departments of Biomedical Sciences and Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California;
authors.forename: Kandarp H
authors.initials: KH
authors.lastname: Shah
authors.affiliation: Departments of Biomedical Sciences and Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California;
authors.forename: Xiao Z
authors.initials: XZ
authors.lastname: Shen
authors.affiliation: Department of Basic Medical Sciences, College of Osteopathic Medicine, Western University of Health Sciences, Pomona, California;
authors.forename: Sebastien
authors.initials: S
authors.lastname: Fuchs
authors.affiliation: Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, Tennessee; and.
authors.forename: Eric
authors.initials: E
authors.lastname: Delpire
authors.affiliation: Laboratory of Experimental Medicine, Alemán Hospital, Buenos Aires, Argentina.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Toblli
authors.affiliation: Departments of Biomedical Sciences and Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California;
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Bernstein
authors.affiliation: Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, California;
authors.forename: Alicia A
authors.initials: AA
authors.lastname: McDonough
authors.affiliation: Departments of Biomedical Sciences and Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California; romer.gonzalezvillalobos@pfizer.com.
authors.forename: Romer A
authors.initials: RA
authors.lastname: Gonzalez-Villalobos
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D005919:Glomerular Filtration Rate; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019331:NG-Nitroarginine Methyl Ester / Q000737:chemistry; D009318:Natriuresis; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D007703:Peptidyl-Dipeptidase A / Q000502:physiology*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D012083:Renin / Q000097:blood; D027981:Symporters / Q000378:metabolism
chemical_list: D027981:Symporters; D000804:Angiotensin II; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D019331:NG-Nitroarginine Methyl Ester
keywords: ACE; L-NAME; hypertension; kidney; mice