Javad Habibi1, Melvin R Hayden2, Carlos M Ferrario3, James R Sowers4, Adam T Whaley-Connell5. 1. Diabetes and Cardiovascular Center, University of Missouri-Columbia School of Medicine, Columbia, Mo., USA ; Department of Medicine, University of Missouri-Columbia School of Medicine, Columbia, Mo., USA ; Division of Endocrinology and Metabolism, University of Missouri-Columbia School of Medicine, Columbia, Mo., USA ; Division of Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, Mo., USA. 2. Diabetes and Cardiovascular Center, University of Missouri-Columbia School of Medicine, Columbia, Mo., USA ; Department of Medicine, University of Missouri-Columbia School of Medicine, Columbia, Mo., USA ; Division of Endocrinology and Metabolism, University of Missouri-Columbia School of Medicine, Columbia, Mo., USA. 3. Division of Wake Forest University School of Medicine, Winston-Salem, N.C., USA. 4. Diabetes and Cardiovascular Center, University of Missouri-Columbia School of Medicine, Columbia, Mo., USA ; Department of Medicine, University of Missouri-Columbia School of Medicine, Columbia, Mo., USA ; Department of Medical Pharmacology and Physiology, University of Missouri-Columbia School of Medicine, Columbia, Mo., USA ; Division of Endocrinology and Metabolism, University of Missouri-Columbia School of Medicine, Columbia, Mo., USA ; Division of Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, Mo., USA. 5. Diabetes and Cardiovascular Center, University of Missouri-Columbia School of Medicine, Columbia, Mo., USA ; Department of Medicine, University of Missouri-Columbia School of Medicine, Columbia, Mo., USA ; Division of Endocrinology and Metabolism, University of Missouri-Columbia School of Medicine, Columbia, Mo., USA ; Division of Nephrology and Hypertension, University of Missouri-Columbia School of Medicine, Columbia, Mo., USA ; Division of Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, Mo., USA.
Abstract
BACKGROUND/AIMS: It is increasingly recognized that there is sexual dimorphism in kidney disease progression; however, this disparity is lost in the presence of diabetes where women progress at a similar rate to men. The renin-angiotensin-aldosterone system (RAAS) is known to regulate diabetes-induced kidney injury, and recent literature would suggest that gender differences exist in RAAS-dependent responses in the kidney. In this regard, these gender differences may be overcome by excessive salt intake. Thereby, we hypothesized that salt would promote proteinuria in transgenic female rats under conditions of excess tissue angiotensin (Ang) II and circulating aldosterone. MATERIALS AND METHODS: We utilized young female transgenic (mRen2)27 (Ren2) rats and Sprague-Dawley (SD) littermates and fed a high-salt diet (4%) over 3 weeks. RESULTS: Compared to SD and Ren2 controls, female Ren2 rats fed a high-salt diet displayed increases in proteinuria, periarterial and interstitial fibrosis as well as ultrastructural evidence of basement membrane thickening, loss of mitochondrial elongation, mitochondrial fragmentation and attenuation of basilar canalicular infoldings. These findings occurred temporally with increases in transforming growth factor-β but not indices of oxidant stress. CONCLUSIONS: Our current data suggest that a diet high in salt promotes progressive kidney injury as measured by proteinuria and fibrosis associated with transforming growth factor-β under conditions of excess tissue Ang II and circulating aldosterone.
BACKGROUND/AIMS: It is increasingly recognized that there is sexual dimorphism in kidney disease progression; however, this disparity is lost in the presence of diabetes where women progress at a similar rate to men. The renin-angiotensin-aldosterone system (RAAS) is known to regulate diabetes-induced kidney injury, and recent literature would suggest that gender differences exist in RAAS-dependent responses in the kidney. In this regard, these gender differences may be overcome by excessive salt intake. Thereby, we hypothesized that salt would promote proteinuria in transgenic female rats under conditions of excess tissue angiotensin (Ang) II and circulating aldosterone. MATERIALS AND METHODS: We utilized young female transgenic (mRen2)27 (Ren2) rats and Sprague-Dawley (SD) littermates and fed a high-salt diet (4%) over 3 weeks. RESULTS: Compared to SD and Ren2 controls, female Ren2 rats fed a high-salt diet displayed increases in proteinuria, periarterial and interstitial fibrosis as well as ultrastructural evidence of basement membrane thickening, loss of mitochondrial elongation, mitochondrial fragmentation and attenuation of basilar canalicular infoldings. These findings occurred temporally with increases in transforming growth factor-β but not indices of oxidant stress. CONCLUSIONS: Our current data suggest that a diet high in salt promotes progressive kidney injury as measured by proteinuria and fibrosis associated with transforming growth factor-β under conditions of excess tissue Ang II and circulating aldosterone.
Authors: Sarah H Lindsey; Liliya M Yamaleyeva; K Bridget Brosnihan; Patricia E Gallagher; Mark C Chappell Journal: Hypertension Date: 2011-08-15 Impact factor: 10.190
Authors: Mihaela C Blendea; David Jacobs; Craig S Stump; Samy I McFarlane; Cristina Ogrin; Gul Bahtyiar; Samir Stas; Pawan Kumar; Quan Sha; Carlos M Ferrario; James R Sowers Journal: Am J Physiol Endocrinol Metab Date: 2004-10-19 Impact factor: 4.310
Authors: Paula-Anahi Arias-Loza; Melanie Muehlfelder; Susan A Elmore; Robert Maronpot; Kai Hu; Hartmut Blode; Christa Hegele-Hartung; Karl Heinrich Fritzemeier; Georg Ertl; Theo Pelzer Journal: Toxicol Pathol Date: 2009-12 Impact factor: 1.902
Authors: James M Luther; Pengcheng Luo; Zuofei Wang; Samuel E Cohen; Hyung-Suk Kim; Agnes B Fogo; Nancy J Brown Journal: Kidney Int Date: 2012-05-23 Impact factor: 10.612
Authors: Yulia N Grigorova; Wen Wei; Natalia Petrashevskaya; Valentina Zernetkina; Ondrej Juhasz; Rachel Fenner; Christian Gilbert; Edward G Lakatta; Joseph I Shapiro; Alexei Y Bagrov; Olga V Fedorova Journal: Int J Mol Sci Date: 2018-10-15 Impact factor: 5.923