Involvement of inducible nitric oxide synthase in renal failure after mild hemorrhage.
The role of iNOS in rats after mild hemorrhaging was examined in this study. A mild hemorrhage (17% of total blood) induced a decrease of systemic blood pressure and heart rate, transiently followed by gradual recovery. The hemorrhage caused expression of renal iNOS mRNA and an increase in systemic NO products at 1 h after bleeding. Serum creatinine and serum urea nitrogen (UN) increased progressively up to 5 h after bleeding. Light microscopic findings showed that some inflammatory monocytes, mainly consisting of neutrophil, often existed in the glomerular capillaries, eosinophilic changes were observed in the cytoplasm at the proximal tubules, and urinary casts existed in the uriniferous space at 5 h after bleeding. The selective iNOS inhibitor, S-methylisothiourea (MTU), suppressed hemorrhagic expression of renal iNOS mRNA and systemic NO products, suppressed the increases of serum creatinine and UN, and improved renal histological aggravations induced by hemorrhaging. We speculated that MTU caused the negative circuit to suppress the renal failure through a decrease of NO generation. These results in the present study showed that iNOS expression induced by mild hemorrhaging at the early phase did participate in the development of renal failure.
Tanaka
Toshiko
T
Department of Forensic Medicine, School of Medicine, University of Occupational and Environmental Health, Iseigaoka 1-1, Yahata-Nishi, Kitakyushu 807-8555, Japan. ttanaka@med.uoeh-u.ac.jp
Sato
Hiroaki
H
Kita
Toshiro
T
Tanaka
Noriyuki
N
D058186:Acute Kidney Injury / Q000201:enzymology*; D000818:Animals; D001806:Blood Urea Nitrogen; D003402:Creatine Kinase / Q000097:blood; D003404:Creatinine / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004804:Eosinophils / Q000473:pathology; D006339:Heart Rate / Q000187:drug effects; D006470:Hemorrhage / Q000378:metabolism*; D007550:Isothiuronium / Q000031:analogs & derivatives* / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000473:pathology; D008297:Male; D008853:Microscopy; D009504:Neutrophils / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014556:Urine / Q000166:cytology
D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D007550:Isothiuronium; D003404:Creatinine; D019001:Nitric Oxide Synthase; D003402:Creatine Kinase; C027744:S-methylisothiopseudouronium