Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1994 Mar;111(3):825–828. doi: 10.1111/j.1476-5381.1994.tb14812.x

Detection of nitric oxide in exhaled air during administration of nitroglycerin in vivo.

M G Persson 1, P Agvald 1, L E Gustafsson 1
PMCID: PMC1910074  PMID: 8019758

Abstract

1. Direct evidence for nitric oxide (NO) formation from nitroglycerin (GTN) was obtained by measurements of NO concentrations in exhaled air in artificially-ventilated, pentobarbitone-anaesthetized rabbits. 2. The concentration of endogenously formed NO was 23 +/- 5 parts per billion (p.p.b.). Infusions of GTN (1-100 micrograms kg-1 min-1, i.v.) induced dose-dependent and biphasic increments in exhaled NO and concomitant reductions in systemic blood pressure. 3. Tolerance to the blood pressure reduction developed in parallel with a decrease in GTN-induced exhaled NO, a pattern which was unaffected by administration of N omega-nitro-L-arginine methyl ester (L-NAME, 30 mg kg-1), L-cysteine (200 mg kg-1), N-acetylcysteine (200 mg kg-1) or glutathione (200 mg kg-1). 4. Intravenous infusions of adenosine (0.7 mg ml-1, 250 microliters kg-1 min-1) and GTN (1 mg ml-1, 250 microliters kg-1 min-1) elicited similar decrements in pulmonary vascular resistance. GTN elicited a substantial increase in exhaled NO (50 +/- 10 p.p.b.) whereas adenosine evoked a markedly smaller increase (7 +/- 1 p.p.b.). L-NAME (30 mg kg-1, i.v.) abolished NO in exhaled air, and evoked an increase in pulmonary vascular resistance from 116 +/- 19 to 147 +/- 9 pulmonary vascular resistance units. After L-NAME the change in pulmonary vascular resistance induced by adenosine or GTN was increased to a similar degree. However, while the increase in exhaled NO induced by nitroglycerin was unaffected, the response to adenosine was abolished. 5. The present data demonstrate that NO is formed from GTN in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
825

Selected References

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

  1. Axelsson K. L., Ahlner J. Nitrate tolerance from a biochemical point of view. Drugs. 1987;33 (Suppl 4):63–68. doi: 10.2165/00003495-198700334-00013. [DOI] [PubMed] [Google Scholar]
  2. Axelsson K. L., Andersson R. G. Tolerance towards nitroglycerin, induced in vivo, is correlated to a reduced cGMP response and an alteration in cGMP turnover. Eur J Pharmacol. 1983 Mar 18;88(1):71–79. doi: 10.1016/0014-2999(83)90393-x. [DOI] [PubMed] [Google Scholar]
  3. Borland C. D., Higenbottam T. W. A simultaneous single breath measurement of pulmonary diffusing capacity with nitric oxide and carbon monoxide. Eur Respir J. 1989 Jan;2(1):56–63. [PubMed] [Google Scholar]
  4. Brien J. F., McLaughlin B. E., Breedon T. H., Bennett B. M., Nakatsu K., Marks G. S. Biotransformation of glyceryl trinitrate occurs concurrently with relaxation of rabbit aorta. J Pharmacol Exp Ther. 1986 May;237(2):608–614. [PubMed] [Google Scholar]
  5. Cossum P. A., Roberts M. S. Metabolite inhibition of nitroglycerin metabolism in sheep tissue homogenates. J Pharm Pharmacol. 1985 Nov;37(11):807–809. doi: 10.1111/j.2042-7158.1985.tb04972.x. [DOI] [PubMed] [Google Scholar]
  6. Diamond J., Blisard K. S. Effects of stimulant and relaxant drugs on tension and cyclic nucleotide levels in canine femoral artery. Mol Pharmacol. 1976 Jul;12(4):668–692. [PubMed] [Google Scholar]
  7. Feelisch M., Noack E. A. Correlation between nitric oxide formation during degradation of organic nitrates and activation of guanylate cyclase. Eur J Pharmacol. 1987 Jul 2;139(1):19–30. doi: 10.1016/0014-2999(87)90493-6. [DOI] [PubMed] [Google Scholar]
  8. Gustafsson L. E., Leone A. M., Persson M. G., Wiklund N. P., Moncada S. Endogenous nitric oxide is present in the exhaled air of rabbits, guinea pigs and humans. Biochem Biophys Res Commun. 1991 Dec 16;181(2):852–857. doi: 10.1016/0006-291x(91)91268-h. [DOI] [PubMed] [Google Scholar]
  9. Ignarro L. J., Lippton H., Edwards J. C., Baricos W. H., Hyman A. L., Kadowitz P. J., Gruetter C. A. Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside and nitric oxide: evidence for the involvement of S-nitrosothiols as active intermediates. J Pharmacol Exp Ther. 1981 Sep;218(3):739–749. [PubMed] [Google Scholar]
  10. Moncada S. The 1991 Ulf von Euler Lecture. The L-arginine: nitric oxide pathway. Acta Physiol Scand. 1992 Jul;145(3):201–227. doi: 10.1111/j.1748-1716.1992.tb09359.x. [DOI] [PubMed] [Google Scholar]
  11. Needleman P., Johnson E. M., Jr Mechanism of tolerance development to organic nitrates. J Pharmacol Exp Ther. 1973 Mar;184(3):709–715. [PubMed] [Google Scholar]
  12. Needleman P., Krantz J. C., Jr The biotransformation of nitroglycerin. Biochem Pharmacol. 1965 Aug;14(8):1225–1230. doi: 10.1016/0006-2952(65)90299-6. [DOI] [PubMed] [Google Scholar]
  13. Noack E., Feelisch M. Molecular mechanisms of nitrovasodilator bioactivation. Basic Res Cardiol. 1991;86 (Suppl 2):37–50. doi: 10.1007/978-3-642-72461-9_5. [DOI] [PubMed] [Google Scholar]
  14. Persson M. G., Gustafsson L. E., Wiklund N. P., Moncada S., Hedqvist P. Endogenous nitric oxide as a probable modulator of pulmonary circulation and hypoxic pressor response in vivo. Acta Physiol Scand. 1990 Dec;140(4):449–457. doi: 10.1111/j.1748-1716.1990.tb09021.x. [DOI] [PubMed] [Google Scholar]
  15. Persson M. G., Wiklund N. P., Gustafsson L. E. Endogenous nitric oxide in single exhalations and the change during exercise. Am Rev Respir Dis. 1993 Nov;148(5):1210–1214. doi: 10.1164/ajrccm/148.5.1210. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES