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This Article Full Text Full Text (PDF) All Versions of this Article: 290/5/F1260    most recent 00150.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Lasaitiene, D. Articles by Friberg, P. Search for Related Content PubMed PubMed Citation Articles by Lasaitiene, D. Articles by Friberg, P.

Tubular mitochondrial alterations in neonatal rats subjected to RAS inhibition

¹Department of Physiology, Institute of Physiology and Pharmacology, ²Department of Clinical Physiology, and ³The Electron Microscopy Unit, Institute of Anatomy and Cell Biology, University of Gothenburg; ⁴Department of Pathology and Cytology, Karolinska Hospital, Stockholm, Sweden; ⁵Institute for Biomedical Research, Kaunas University of Medicine, Kaunas; ⁶Environmental Research Center, Faculty of Nature Science, Vytautas Magnus University, Kaunas, Lithuania; and ⁷Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

Submitted 12 April 2005 ; accepted in final form 17 October 2005

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.

renal development; cytochrome c; cytochrome a; succinate dehydrogenase; Na⁺-K⁺-adenosinetriphosphatase