title: Tubular mitochondrial alterations in neonatal rats subjected to RAS inhibition.
abstract: Pharmacological interruption of the angiotensin II (ANG II) type 1 receptor signaling during nephrogenesis in rats perturbs renal tubular development. This study aimed to further investigate tubular developmental defects in neonatal rats subjected to ANG II inhibition with enalapril. We evaluated tubular ultrastructural changes using electron microscopy and estimated spectrophotometrically activity or concentrations of succinate dehydrogenase (SDH), cytochromes a and c, which are components of mitochondrial respiratory chain, on postnatal days 2 and 9 (PD2 and PD9). Renal expression of sodium-potassium adenosinetriphosphatase (Na(+)-K(+)-ATPase) and two reflectors of mitochondrial biogenesis [mitochondrial transcription factor A (TFAM) and translocase of outer mitochondrial membrane 20 (TOM20)] also were studied using Western immunoblotting and immunohistochemistry. Enalapril disrupted inner mitochondrial membranes of developing cortical and medullary tubular cells on PD2 and PD9. These findings were paralleled by impaired mitochondrial respiratory function, as revealed from the changes in components of the mitochondrial respiratory chain, such as decreased cytochrome c level in the cortex and medulla on PD2 and PD9, decreased cytochrome a level in the cortex and medulla on PD2, and diminished cortical SDH activity on PD2 and PD9. Moreover, tubular expression of the most active energy-consuming pump Na(+)-K(+)-ATPase was decreased by enalapril treatment. Renal expression of TFAM and TOM20 was not altered by neonatal enalapril treatment. Because nephrogenesis is a highly energy-demanding biological process, with the energy being utilized for renal growth and transport activities, the structural-functional alterations of the mitochondria induced by neonatal enalapril treatment may provide the propensity for the tubular developmental defect.
authors.affiliation: Dept. of Clinical Physiology, Univ. of Gothenburg, S-413 45 Gothenburg, Sweden. daina.lasaitiene@kidney.med.gu.se
authors.forename: Daina
authors.initials: D
authors.lastname: Lasaitiene
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
authors.forename: Vida
authors.initials: V
authors.lastname: Mildaziene
authors.forename: Zita
authors.initials: Z
authors.lastname: Nauciene
authors.forename: Birgitta
authors.initials: B
authors.lastname: Sundelin
authors.forename: Bengt R
authors.initials: BR
authors.lastname: Johansson
authors.forename: Masato
authors.initials: M
authors.lastname: Yano
authors.forename: Peter
authors.initials: P
authors.lastname: Friberg
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects* / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D004656:Enalapril / Q000009:adverse effects* / Q000494:pharmacology; D007150:Immunohistochemistry; D007684:Kidney Tubules / Q000187:drug effects / Q000254:growth & development* / Q000648:ultrastructure; D008854:Microscopy, Electron; D008928:Mitochondria / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D004656:Enalapril; D000254:Sodium-Potassium-Exchanging ATPase