Increased oxidative stress in rats with chronic nitric oxide depletion: measurement of urinary 8-hydroxy-2'-deoxyguanosine excretion.
Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) has been reported to serve as a sensitive biomarker of oxidative stress. We examined the effect of chronic blockade of nitric oxide (NO) on urinary excretion of 8-OHdG in rats. Two types of NO synthase inhibitor were used: N(G)-nitro-L-arginine methyl ester (L-NAME) as a non-selective inhibitor and aminoguanidine (AG) as a selective inhibitor of the inducible isoform. Oral administration of L-NAME (20, 50 and 80 mg/dl of drinking water), but not AG (400 mg/dl), for 4 weeks induced systemic hypertension and a significant reduction in urinary excretion of NO2-/NO3-. Rats treated with L-NAME also showed a significant increase in urinary 8-OHdG excretion compared with the control animals. The effects of L-NAME (50 mg/dl) on blood pressure and urinary excretion of NO2/NO3- and 8-OHdG were restored by a large dose of L-arginine (2.0 g/dl). Chronic AG administration did not significantly alter urinary 8-OHdG excretion. On combining all the data, there was a significant negative correlation between urinary NO2-/NO,- and 8-OHdG. These observations suggest the importance of constitutive NO synthase activity in the maintenance of oxidant buffering capacity in rats. Oral administration of L-NAME may serve as a model of hypertension due to chronic NO deficiency with increased oxidative stress.
Tsukahara
H
H
Department of Pediatrics, Fukui Medical University,Japan. htsuka@fmsrsa.fukui-med.ac.jp
Hiraoka
M
M
Kobata
R
R
Hata
I
I
Ohshima
Y
Y
Jiang
M Z
MZ
Noiri
E
E
Mayumi
M
M
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine*; D004326:Drinking; D007677:Kidney Function Tests; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009569:Nitric Oxide / Q000378:metabolism* / Q000652:urine; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D009569:Nitric Oxide; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D019331:NG-Nitroarginine Methyl Ester