Original Research Papers

Inflammation Research

, Volume 45, Issue 6, pp 272-276

First online:

Failure of L-NAME to cause inhibition of nitric oxide synthesis: Role of inducible nitric oxide synthase

  • M. J. S. MillerAffiliated withDepartment of Pediatrics, Louisiana State University Medical CenterStanley S. Scott Cancer Center
  • , J. H. ThompsonAffiliated withDepartment of Pediatrics, Louisiana State University Medical Center
  • , X. LiuAffiliated withDepartment of Pediatrics, Louisiana State University Medical Center
  • , S. Eloby-ChildressAffiliated withDepartment of Pediatrics, Louisiana State University Medical Center
  • , H. Sadowska-KrowickaAffiliated withDepartment of Pediatrics, Louisiana State University Medical Center
  • , X-Jing ZhangAffiliated withDepartment of Pediatrics, Louisiana State University Medical Center
  • , D. A. ClarkAffiliated withDepartment of Pediatrics, Louisiana State University Medical Center

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Abstract

We addressed the hypothesis that administration of nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) does not result in a sustained suppression of nitric oxide (NO) synthesis, because of a compensatory expression of inducible nitric oxide synthase (iNOS). L-NAME was administered in the drinking water (0.1–1.0 mg/ml) for 7 days to guinea pigs and rats. Nitric oxide synthesis was assessed by [1] ex vivo formation of nitrite in blood vessels and intestine [2] tissue levels of cGMP [3] iNOS gene expression by RT-PCR [4] NADPH diaphorase staining [5] direct assessment of NO release in tissue explants using a microelectrode/electrochemical detection system. Chronic L-NAME administration elevated intestinal cGMP and nitrite levels in guinea pigs (p<0.05). In rats, intestinal nitrite levels were comparable in control and L-NAME treatment groups, whereas direct assessment of NO release defined a marked increase in the L-NAME group. Chronic L-NAME resulted in an induction of iNOS gene expression in rats and guinea pigs and novel sites of NADPH diaphorase staining in the intestine. We conclude that iNOS expression is responsible for a compensatory increase or normalization of NO synthesis during sustained administration of L-NAME.

Key words

Nitric oxide Inflammation Gene expression Intestine