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. 1994 Oct;113(2):496–498. doi: 10.1111/j.1476-5381.1994.tb17016.x

Effect of nitric oxide gas on the generation of nitric oxide by isolated blood vessels: implications for inhalation therapy.

R J Kiff 1, D W Moss 1, S Moncada 1
PMCID: PMC1510112  PMID: 7530572

Abstract

1. We have investigated, using rat aortic rings, whether exogenous nitric oxide (NO) gas affects the activity or expression of the inducible, Ca(2+)-independent NO synthase. 2. Incubation of rings with lipopolysaccharide (LPS, S. typhosa) for 6 h resulted in a gradual loss of tissue tone, a time-dependent reduction in constrictor response to phenylephrine and significant expression and activity of Ca(2+)-independent NO synthase. 3. Following incubation of LPS-treated rings with NO gas, the expression of inducible NO synthase mRNA was still observed, although the enzyme activity was significantly reduced and there was no reduction in the response to phenylephrine. 4. Therefore, NO gas can inhibit the action but not the induction of an NO synthase likely to play a role in inflammatory states such as adult respiratory distress syndrome (ARDS). 5. These observations may explain the rebound phenomenon observed in some ARDS patients following inhalation therapy with NO gas.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Assreuy J., Cunha F. Q., Liew F. Y., Moncada S. Feedback inhibition of nitric oxide synthase activity by nitric oxide. Br J Pharmacol. 1993 Mar;108(3):833–837. doi: 10.1111/j.1476-5381.1993.tb12886.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Buga G. M., Griscavage J. M., Rogers N. E., Ignarro L. J. Negative feedback regulation of endothelial cell function by nitric oxide. Circ Res. 1993 Nov;73(5):808–812. doi: 10.1161/01.res.73.5.808. [DOI] [PubMed] [Google Scholar]
  3. Gerlach H., Pappert D., Lewandowski K., Rossaint R., Falke K. J. Long-term inhalation with evaluated low doses of nitric oxide for selective improvement of oxygenation in patients with adult respiratory distress syndrome. Intensive Care Med. 1993;19(8):443–449. doi: 10.1007/BF01711084. [DOI] [PubMed] [Google Scholar]
  4. Gerlach H., Rossaint R., Pappert D., Falke K. J. Time-course and dose-response of nitric oxide inhalation for systemic oxygenation and pulmonary hypertension in patients with adult respiratory distress syndrome. Eur J Clin Invest. 1993 Aug;23(8):499–502. doi: 10.1111/j.1365-2362.1993.tb00797.x. [DOI] [PubMed] [Google Scholar]
  5. Jones D. K., Higenbottam T. W., Wallwork J. Treatment of primary pulmonary hypertension intravenous epoprostenol (prostacyclin). Br Heart J. 1987 Mar;57(3):270–278. doi: 10.1136/hrt.57.3.270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Moncada S., Rees D. D., Schulz R., Palmer R. M. Development and mechanism of a specific supersensitivity to nitrovasodilators after inhibition of vascular nitric oxide synthesis in vivo. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2166–2170. doi: 10.1073/pnas.88.6.2166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Naeije R., Mélot C., Mols P., Hallemans R. Effects of vasodilators on hypoxic pulmonary vasoconstriction in normal man. Chest. 1982 Oct;82(4):404–410. doi: 10.1378/chest.82.4.404. [DOI] [PubMed] [Google Scholar]
  8. Palmer R. M., Moncada S. A novel citrulline-forming enzyme implicated in the formation of nitric oxide by vascular endothelial cells. Biochem Biophys Res Commun. 1989 Jan 16;158(1):348–352. doi: 10.1016/s0006-291x(89)80219-0. [DOI] [PubMed] [Google Scholar]
  9. Rees D. D., Cellek S., Palmer R. M., Moncada S. Dexamethasone prevents the induction by endotoxin of a nitric oxide synthase and the associated effects on vascular tone: an insight into endotoxin shock. Biochem Biophys Res Commun. 1990 Dec 14;173(2):541–547. doi: 10.1016/s0006-291x(05)80068-3. [DOI] [PubMed] [Google Scholar]
  10. Rogers N. E., Ignarro L. J. Constitutive nitric oxide synthase from cerebellum is reversibly inhibited by nitric oxide formed from L-arginine. Biochem Biophys Res Commun. 1992 Nov 30;189(1):242–249. doi: 10.1016/0006-291x(92)91550-a. [DOI] [PubMed] [Google Scholar]
  11. Rossaint R., Falke K. J., López F., Slama K., Pison U., Zapol W. M. Inhaled nitric oxide for the adult respiratory distress syndrome. N Engl J Med. 1993 Feb 11;328(6):399–405. doi: 10.1056/NEJM199302113280605. [DOI] [PubMed] [Google Scholar]

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