title: Increased mitochondrial activity in renal proximal tubule cells from young spontaneously hypertensive rats.
abstract: Renal proximal tubule cells from spontaneously hypertensive rats (SHR), compared with normotensive Wistar-Kyoto rats (WKY), have increased oxidative stress. The contribution of mitochondrial oxidative phosphorylation to the subsequent hypertensive phenotype remains unclear. We found that renal proximal tubule cells from SHR, relative to WKY, had significantly higher basal oxygen consumption rates, adenosine triphosphate synthesis-linked oxygen consumption rates, and maximum and reserve respiration. These bioenergetic parameters indicated increased mitochondrial function in renal proximal tubule cells from SHR compared with WKY. Pyruvate dehydrogenase complex activity was consistently higher in both renal proximal tubule cells and cortical homogenates from SHR than those from WKY. Treatment for 6 days with dichloroacetate, an inhibitor of pyruvate dehydrogenase kinase, significantly increased renal pyruvate dehydrogenase complex activity and systolic blood pressure in 3-week-old WKY and SHR. Therefore, mitochondrial oxidative phosphorylation is higher in renal proximal tubule cells from SHR compared with WKY. Thus, the pyruvate dehydrogenase complex is a determinant of increased mitochondrial metabolism that could be a causal contributor to the hypertension in SHR.
authors.affiliation: 1] Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA [2] Kidney Disease Section, Kidney Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Hewang
authors.initials: H
authors.lastname: Lee
authors.affiliation: Kidney Disease Section, Kidney Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Abe
authors.affiliation: College of Medicine, Dankook University, Cheonan-si, Chungcheongnam-do, Korea.
authors.forename: Icksoo
authors.initials: I
authors.lastname: Lee
authors.affiliation: Kidney Disease Section, Kidney Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Shashi
authors.initials: S
authors.lastname: Shrivastav
authors.affiliation: Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Annabelle P
authors.initials: AP
authors.lastname: Crusan
authors.affiliation: Center for Molecular Medicine and Genetics and Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Maik
authors.initials: M
authors.lastname: Hüttemann
authors.affiliation: Department of Physiology and Biophysics, Case Western Reserve University, School of Medicine, Cleveland, Ohio, USA.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hopfer
authors.affiliation: Department of Pathology, University of Virginia Health Sciences Center, Charlottesville, Virginia, USA.
authors.forename: Robin A
authors.initials: RA
authors.lastname: Felder
authors.affiliation: Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Laureano D
authors.initials: LD
authors.lastname: Asico
authors.affiliation: Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Ines
authors.initials: I
authors.lastname: Armando
authors.affiliation: Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Jose
authors.affiliation: Kidney Disease Section, Kidney Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Kopp
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D002478:Cells, Cultured; D006019:Glycolysis; D006973:Hypertension / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D011768:Pyruvate Dehydrogenase Complex; D000255:Adenosine Triphosphate