Nitric oxide synthase expression in hypertension induced by inhibition of glutathione synthase.
Induction of chronic oxidative stress by glutathione (GSH) depletion has been shown to cause hypertension in normal rats. This was accompanied by and perhaps in part due to inactivation and sequestration of NO by reactive oxygen species (ROS), leading to diminished NO bioavailability. This study was designed to examine renal histology, nitric oxide synthase (NOS) isotype expression, and nitrotyrosine distribution in this model. Sprague-Dawley rats were subjected to oxidative stress by administration of the GSH synthase inhibitor buthionine sulfoximine (BSO; 30 mM/l in drinking water) for 2 weeks. The controls were given tap water. Blood pressure, renal histology, tissue expression of endothelial and inducible NOS (eNOS and iNOS) and nitrotyrosine, tissue GSH content, and urinary excretion of NO metabolites (NOx) were examined. The BSO-treated group showed a 3-fold decrease in tissue GSH content, a marked elevation in blood pressure, and a significant reduction in the urinary excretion of NOx. Histological examination of kidneys revealed no significant abnormalities in either group. In addition, no significant differences were observed in either intensities or localizations of eNOS and iNOS in the kidney. However, the BSO-treated group exhibited intense accumulation in the renal tissue of nitrotyrosine, which is the footprint of NO oxidation by ROS. These observations suggest that oxidative stress-induced hypertension is not caused by either structural abnormality of or depressed NOS expression by the kidney in this model. Instead, it is associated with and perhaps partially related to enhanced renal NO inactivation by ROS and diminished NO bioavailability.
Zhou
Xin J
XJ
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9073, USA. zhou@utsouthwestern.edu
Vaziri
Nosratola D
ND
Wang
Xiu Q
XQ
Silva
Fred G
FG
Laszik
Zoltan
Z
D000818:Animals; D001120:Arginine / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005981:Glutathione Synthase / Q000037:antagonists & inhibitors*; D006973:Hypertension / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D007124:Immunoenzyme Techniques; D007668:Kidney / Q000201:enzymology* / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism / Q000652:urine; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D005981:Glutathione Synthase