title: Salt Sensitivity in Response to Renal Injury Requires Renal Angiotensin-Converting Enzyme.
abstract: Recent evidence indicates that salt-sensitive hypertension can result from a subclinical injury that impairs the kidneys' capacity to properly respond to a high-salt diet. However, how this occurs is not well understood. Here, we showed that although previously salt-resistant wild-type mice became salt sensitive after the induction of renal injury with the nitric oxide synthase inhibitor Nω-nitro-l-arginine methyl ester hydrochloride; mice lacking renal angiotensin-converting enzyme, exposed to the same insult, did not become hypertensive when faced with a sodium load. This is because the activity of renal angiotensin-converting enzyme plays a critical role in (1) augmenting the local pool of angiotensin II and (2) the establishment of the antinatriuretic state via modulation of glomerular filtration rate and sodium tubular transport. Thus, this study demonstrates that the presence of renal angiotensin-converting enzyme plays a pivotal role in the development of salt sensitivity in response to renal injury.
authors.affiliation: From the Departments of Biomedical Sciences and Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA (J.F.G., K.E.B., T.J., X.Z.S., R.A.G.-V.); Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles (J.H., A.A.M.); Laboratory of Experimental Medicine, Hospital Alemán, Buenos Aires, Argentina (J.E.T.); Servicio de Nefrología, Hospital Universitario de Maracaibo, Maracaibo, Venezuela (B.R.-I.); and Physiology Group, DSRD/Global Safety Pharmacology, Pfizer Inc., Groton, CT (R.A.G.-V.).
authors.forename: Jorge F
authors.initials: JF
authors.lastname: Giani
authors.affiliation: From the Departments of Biomedical Sciences and Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA (J.F.G., K.E.B., T.J., X.Z.S., R.A.G.-V.); Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles (J.H., A.A.M.); Laboratory of Experimental Medicine, Hospital Alemán, Buenos Aires, Argentina (J.E.T.); Servicio de Nefrología, Hospital Universitario de Maracaibo, Maracaibo, Venezuela (B.R.-I.); and Physiology Group, DSRD/Global Safety Pharmacology, Pfizer Inc., Groton, CT (R.A.G.-V.).
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Bernstein
authors.affiliation: From the Departments of Biomedical Sciences and Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA (J.F.G., K.E.B., T.J., X.Z.S., R.A.G.-V.); Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles (J.H., A.A.M.); Laboratory of Experimental Medicine, Hospital Alemán, Buenos Aires, Argentina (J.E.T.); Servicio de Nefrología, Hospital Universitario de Maracaibo, Maracaibo, Venezuela (B.R.-I.); and Physiology Group, DSRD/Global Safety Pharmacology, Pfizer Inc., Groton, CT (R.A.G.-V.).
authors.forename: Tea
authors.initials: T
authors.lastname: Janjulia
authors.affiliation: From the Departments of Biomedical Sciences and Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA (J.F.G., K.E.B., T.J., X.Z.S., R.A.G.-V.); Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles (J.H., A.A.M.); Laboratory of Experimental Medicine, Hospital Alemán, Buenos Aires, Argentina (J.E.T.); Servicio de Nefrología, Hospital Universitario de Maracaibo, Maracaibo, Venezuela (B.R.-I.); and Physiology Group, DSRD/Global Safety Pharmacology, Pfizer Inc., Groton, CT (R.A.G.-V.).
authors.forename: Jiyang
authors.initials: J
authors.lastname: Han
authors.affiliation: From the Departments of Biomedical Sciences and Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA (J.F.G., K.E.B., T.J., X.Z.S., R.A.G.-V.); Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles (J.H., A.A.M.); Laboratory of Experimental Medicine, Hospital Alemán, Buenos Aires, Argentina (J.E.T.); Servicio de Nefrología, Hospital Universitario de Maracaibo, Maracaibo, Venezuela (B.R.-I.); and Physiology Group, DSRD/Global Safety Pharmacology, Pfizer Inc., Groton, CT (R.A.G.-V.).
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Toblli
authors.affiliation: From the Departments of Biomedical Sciences and Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA (J.F.G., K.E.B., T.J., X.Z.S., R.A.G.-V.); Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles (J.H., A.A.M.); Laboratory of Experimental Medicine, Hospital Alemán, Buenos Aires, Argentina (J.E.T.); Servicio de Nefrología, Hospital Universitario de Maracaibo, Maracaibo, Venezuela (B.R.-I.); and Physiology Group, DSRD/Global Safety Pharmacology, Pfizer Inc., Groton, CT (R.A.G.-V.).
authors.forename: Xiao Z
authors.initials: XZ
authors.lastname: Shen
authors.affiliation: From the Departments of Biomedical Sciences and Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA (J.F.G., K.E.B., T.J., X.Z.S., R.A.G.-V.); Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles (J.H., A.A.M.); Laboratory of Experimental Medicine, Hospital Alemán, Buenos Aires, Argentina (J.E.T.); Servicio de Nefrología, Hospital Universitario de Maracaibo, Maracaibo, Venezuela (B.R.-I.); and Physiology Group, DSRD/Global Safety Pharmacology, Pfizer Inc., Groton, CT (R.A.G.-V.).
authors.forename: Bernardo
authors.initials: B
authors.lastname: Rodriguez-Iturbe
authors.affiliation: From the Departments of Biomedical Sciences and Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA (J.F.G., K.E.B., T.J., X.Z.S., R.A.G.-V.); Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles (J.H., A.A.M.); Laboratory of Experimental Medicine, Hospital Alemán, Buenos Aires, Argentina (J.E.T.); Servicio de Nefrología, Hospital Universitario de Maracaibo, Maracaibo, Venezuela (B.R.-I.); and Physiology Group, DSRD/Global Safety Pharmacology, Pfizer Inc., Groton, CT (R.A.G.-V.).
authors.forename: Alicia A
authors.initials: AA
authors.lastname: McDonough
authors.affiliation: From the Departments of Biomedical Sciences and Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA (J.F.G., K.E.B., T.J., X.Z.S., R.A.G.-V.); Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles (J.H., A.A.M.); Laboratory of Experimental Medicine, Hospital Alemán, Buenos Aires, Argentina (J.E.T.); Servicio de Nefrología, Hospital Universitario de Maracaibo, Maracaibo, Venezuela (B.R.-I.); and Physiology Group, DSRD/Global Safety Pharmacology, Pfizer Inc., Groton, CT (R.A.G.-V.). romer.gonzalezvillalobos@pfizer.com.
authors.forename: Romer A
authors.initials: RA
authors.lastname: Gonzalez-Villalobos
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D006973:Hypertension / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D019331:NG-Nitroarginine Methyl Ester; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*; D017673:Sodium Chloride, Dietary
chemical_list: D017673:Sodium Chloride, Dietary; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; D019331:NG-Nitroarginine Methyl Ester
keywords: angiotensin-converting enzyme; diet; glomerular filtration rate; hypertension; inflammation