Null Mutation of the Nicotinamide Adenine Dinucleotide Phosphate–Oxidase Subunit p67phox Protects the Dahl-S Rat From Salt-Induced Reductions in Medullary Blood Flow and Glomerular Filtration Rate

作者: Louise C. Evans , Robert P. Ryan , Elizabeth Broadway , Meredith M. Skelton , Theresa Kurth

DOI: 10.1161/HYPERTENSIONAHA.114.04468

关键词:

摘要: Null mutations in the p67 phox subunit of nicotinamide adenine dinucleotide phosphate–oxidase confer protection from salt sensitivity on Dahl salt-sensitive rats. Here, we track sequential changes medullary blood flow (MBF), glomerular filtration rate (GFR), urinary protein, and mean arterial pressure SS null rats wild-type littermates during 21 days 4.0% NaCl high-salt (HS) diet. Optical fibers were implanted renal medulla MBF was measured conscious by laser Doppler flowmetry. Separate groups prepared with femoral venous catheters GFR transcutaneous assessment fluorescein isothiocyanate-sinistrin disappearance curves. Mean telemetry. In rats, HS caused a rapid reduction MBF, which significantly lower than control values day-6. Reduced associated progressive increase pressure, averaging 170±5 mm Hg day-21. A significant evident day-14 HS, after onset hypertension reduced MBF. contrast, had no effect pressor response to sodium blunted, 150±3 day-21 HS. maintained throughout study proteinuria reduced. summary, when is not functional does cause attenuated, consequently injury maintained.

参考文章(41)
Sanders Pw, Kirk Ka, Chen Py, St John Pl, Abrahamson Dr, Hypertensive nephrosclerosis in the Dahl/Rapp rat. Initial sites of injury and effect of dietary L-arginine supplementation. Laboratory Investigation. ,vol. 68, pp. 174- 184 ,(1993)
James L. Pirkle, Barry I. Freedman, Hypertension and chronic kidney disease: controversies in pathogenesis and treatment. The Italian journal of urology and nephrology. ,vol. 65, pp. 37- 50 ,(2013)
Ai-Ping Zou, Ningjun Li, Allen W. Cowley, Production and actions of superoxide in the renal medulla. Hypertension. ,vol. 37, pp. 547- 553 ,(2001) , 10.1161/01.HYP.37.2.547
Ayako Makino, Meredith M. Skelton, Ai-Ping Zou, Allen W. Cowley, Increased Renal Medullary H2O2 Leads to Hypertension Hypertension. ,vol. 42, pp. 25- 30 ,(2003) , 10.1161/01.HYP.0000074903.96928.91
Niu Tian, Rebecca S. Moore, William E. Phillips, Lin Lin, Sharkeshia Braddy, Janelle S. Pryor, Rachel L. Stockstill, Michael D. Hughson, R. Davis Manning, NADPH oxidase contributes to renal damage and dysfunction in Dahl salt-sensitive hypertension American Journal of Physiology-regulatory Integrative and Comparative Physiology. ,vol. 295, ,(2008) , 10.1152/AJPREGU.90650.2008
Myron H. Weinberger, Salt Sensitivity of Blood Pressure in Humans Hypertension. ,vol. 27, pp. 481- 490 ,(1996) , 10.1161/01.HYP.27.3.481
R. Davis Manning Jr., Niu Tian, Shumei Meng, Oxidative stress and antioxidant treatment in hypertension and the associated renal damage. American Journal of Nephrology. ,vol. 25, pp. 311- 317 ,(2005) , 10.1159/000086411
Yuichi Maehara, Kei Miyano, Hideki Sumimoto, Role for the first SH3 domain of p67phox in activation of superoxide-producing NADPH oxidases Biochemical and Biophysical Research Communications. ,vol. 379, pp. 589- 593 ,(2009) , 10.1016/J.BBRC.2008.12.112