Increased oxidative stress in rats with chronic nitric oxide depletion: Measurement of urinary 8-hydroxy-2'-deoxyguanosine excretion

Hirokazu Tsukahara, Masahiro Hiraoka, Ritsuyo Kobata, Ikue Hata, Yusei Ohshima, Mi Zu Jiang, Eisei Noiri, Mitsufumi Mayumi

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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-Larginine methyl ester (L-NAME) as a non-selective inhibitor and aminoguanidine (AG) as aselective 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-/NO3- 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.

Original languageEnglish
Pages (from-to)23-28
Number of pages6
JournalRedox Report
Volume5
Issue number1
DOIs
Publication statusPublished - Jan 1 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical

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