Which comes first: renal inflammation or oxidative stress in spontaneously hypertensive rats?
The present study was undertaken to identify whether inflammation or oxidative stress is the primary abnormality in the kidney in spontaneously hypertensive rats (SHR). Renal inflammation and oxidative stress were evaluated in 2- and 3-week-old prehypertensive SHR and age-matched genetically normotensive control Wistar-Kyoto (WKY) rats. Blood pressure was similar in WKY and SHR rats at 2 and 3 weeks, of age. Renal inflammation (macrophage and nuclear factor-kappaB) was elevated in SHR at 3 weeks, but not at 2 weeks, of age compared with age-matched WKY rats. Renal oxidative stress (nitrotyrosine, 8-hydroxy-2'-deoxyguanosine and p47phox) was also clearly elevated in 3-week-old SHR compared with age-matched WKY rats. Additionally, NADPH oxidase subunit p47phox was found elevated in 2-week-old SHR compared to age-matched WKY rats. Moreover, antioxidant (N-acetyl-L-cysteine and Tempol) treatment reduced renal inflammation in prehypertensive SHR. We therefore conclude that the oxidative stress appears before inflammation as a primary abnormality in the kidney in prehypertensive SHR.
Biswas
Subrata K
SK
Division of Nephrology, Renal Pathophysiology Laboratory, Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas (UNICAMP), 13084-971 Campinas, Sao Paulo, Brazil.
de Faria
Jose B Lopes
JB
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000111:Acetylcysteine / Q000627:therapeutic use; D000367:Age Factors; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001794:Blood Pressure; D003497:Cyclic N-Oxides / Q000627:therapeutic use; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D004195:Disease Models, Animal; D018450:Disease Progression; D005978:Glutathione / Q000032:analysis; D006973:Hypertension / Q000188:drug therapy / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D007672:Kidney Cortex / Q000378:metabolism; D008297:Male; D019255:NADPH Oxidases / Q000032:analysis; D009393:Nephritis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D018384:Oxidative Stress; D051381:Rats; D011918:Rats, Inbred SHR / Q000378:metabolism*; D011921:Rats, Inbred WKY; D013113:Spin Labels; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D000975:Antioxidants; D003497:Cyclic N-Oxides; D013113:Spin Labels; C002744:3-nitrotyrosine; D014443:Tyrosine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D003849:Deoxyguanosine; D005978:Glutathione; C001803:tempol; D000111:Acetylcysteine