Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1993 Jun;109(2):587–591. doi: 10.1111/j.1476-5381.1993.tb13611.x

Impairment of pulmonary-artery endothelium-dependent relaxation in chronic obstructive lung disease is not due to dysfunction of endothelial cell membrane receptors nor to L-arginine deficiency.

A T Dinh-Xuan 1, J Pepke-Zaba 1, A Y Butt 1, G Cremona 1, T W Higenbottam 1
PMCID: PMC2175681  PMID: 7689396

Abstract

1. Endothelium-dependent relaxation mediated by endothelium-derived relaxing factor (EDRF) or nitric oxide (NO), is impaired in pulmonary arteries (PA) of hypoxic patients with chronic obstructive lung disease (COLD). To determine the mechanisms responsible for this impairment, we compared the response of rings of isolated PA from 12 COLD patients and 8 controls to the endothelium-dependent vasodilators acetylcholine (ACh), adenosine diphosphate (ADP), and the calcium ionophore, A23187. The response of PA rings to the endothelium-independent nitro-vasodilator sodium nitroprusside (SNP) was also studied in both groups. The PA rings had been pre-contracted by the alpha-adrenoceptor agonist phenylephrine (PE). 2. Endothelium-dependent relaxation was significantly reduced in PA rings from COLD patients as compared with controls when tested with ACh (37.8 +/- 8.8% vs 73.4 +/- 7.9%), ADP (38.4 +/- 6.7% vs 80 +/- 5.6%), and the calcium ionophore, A23187 (35.8 +/- 6.1% vs 87 +/- 6.6%). Relaxation with SNP was, however, significantly greater in PA rings from COLD patients (99.4 +/- 0.6% vs 90.3 +/- 3.1%), as was the contractile response to PE (1.91 +/- 0.21 g vs 1.33 +/- 0.15 g). Pretreatment with the specific inhibitor of NO formation, NG-monomethyl-L-arginine (L-NMMA; 10(-4) M) significantly reduced the relaxation to ACh in all PA rings. This inhibition could be reversed by L-arginine (10(-3) M), the substrate for NO synthesis. Pretreatment with L-arginine alone, however, did not restore the impaired endothelium-dependent relaxation of PA rings from COLD patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
591

Selected References

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

  1. Abman S. H., Chatfield B. A., Rodman D. M., Hall S. L., McMurtry I. F. Maturational changes in endothelium-derived relaxing factor activity of ovine pulmonary arteries in vitro. Am J Physiol. 1991 Apr;260(4 Pt 1):L280–L285. doi: 10.1152/ajplung.1991.260.4.L280. [DOI] [PubMed] [Google Scholar]
  2. Adnot S., Raffestin B., Eddahibi S., Braquet P., Chabrier P. E. Loss of endothelium-dependent relaxant activity in the pulmonary circulation of rats exposed to chronic hypoxia. J Clin Invest. 1991 Jan;87(1):155–162. doi: 10.1172/JCI114965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bossaller C., Habib G. B., Yamamoto H., Williams C., Wells S., Henry P. D. Impaired muscarinic endothelium-dependent relaxation and cyclic guanosine 5'-monophosphate formation in atherosclerotic human coronary artery and rabbit aorta. J Clin Invest. 1987 Jan;79(1):170–174. doi: 10.1172/JCI112779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dinh Xuan A. T., Higenbottam T. W., Clelland C., Pepke-Zaba J., Cremona G., Wallwork J. Impairment of pulmonary endothelium-dependent relaxation in patients with Eisenmenger's syndrome. Br J Pharmacol. 1990 Jan;99(1):9–10. doi: 10.1111/j.1476-5381.1990.tb14643.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dinh Xuan A. T., Higenbottam T. W., Clelland C., Pepke-Zaba J., Wells F. C., Wallwork J. Acetylcholine and adenosine diphosphate cause endothelium-dependent relaxation of isolated human pulmonary arteries. Eur Respir J. 1990 Jun;3(6):633–638. [PubMed] [Google Scholar]
  6. Dinh Xuan A. T., Higenbottam T. W., Pepke-Zaba J., Clelland C., Wallwork J. Reduced endothelium-dependent relaxation of cystic fibrosis pulmonary arteries. Eur J Pharmacol. 1989 Apr 25;163(2-3):401–403. doi: 10.1016/0014-2999(89)90217-3. [DOI] [PubMed] [Google Scholar]
  7. Dinh-Xuan A. T., Higenbottam T. W., Clelland C. A., Pepke-Zaba J., Cremona G., Butt A. Y., Large S. R., Wells F. C., Wallwork J. Impairment of endothelium-dependent pulmonary-artery relaxation in chronic obstructive lung disease. N Engl J Med. 1991 May 30;324(22):1539–1547. doi: 10.1056/NEJM199105303242203. [DOI] [PubMed] [Google Scholar]
  8. Furchgott R. F., Zawadzki J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373–376. doi: 10.1038/288373a0. [DOI] [PubMed] [Google Scholar]
  9. Higenbottam T., Otulana B. A., Wallwork J. Transplantation of the lung. Eur Respir J. 1990 May;3(5):594–605. [PubMed] [Google Scholar]
  10. Johns R. A., Linden J. M., Peach M. J. Endothelium-dependent relaxation and cyclic GMP accumulation in rabbit pulmonary artery are selectively impaired by moderate hypoxia. Circ Res. 1989 Dec;65(6):1508–1515. doi: 10.1161/01.res.65.6.1508. [DOI] [PubMed] [Google Scholar]
  11. Kwon N. S., Nathan C. F., Gilker C., Griffith O. W., Matthews D. E., Stuehr D. J. L-citrulline production from L-arginine by macrophage nitric oxide synthase. The ureido oxygen derives from dioxygen. J Biol Chem. 1990 Aug 15;265(23):13442–13445. [PubMed] [Google Scholar]
  12. Magee F., Wright J. L., Wiggs B. R., Paré P. D., Hogg J. C. Pulmonary vascular structure and function in chronic obstructive pulmonary disease. Thorax. 1988 Mar;43(3):183–189. doi: 10.1136/thx.43.3.183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
  14. Palmer R. M., Ashton D. S., Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature. 1988 Jun 16;333(6174):664–666. doi: 10.1038/333664a0. [DOI] [PubMed] [Google Scholar]
  15. Palmer R. M., Ferrige A. G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11;327(6122):524–526. doi: 10.1038/327524a0. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Pieper G. M., Gross G. J. Selective impairment of endothelium-dependent relaxation by oxygen-derived free radicals: distinction between receptor versus nonreceptor mediators. Blood Vessels. 1989;26(1):44–47. [PubMed] [Google Scholar]
  18. Rees D. D., Palmer R. M., Hodson H. F., Moncada S. A specific inhibitor of nitric oxide formation from L-arginine attenuates endothelium-dependent relaxation. Br J Pharmacol. 1989 Feb;96(2):418–424. doi: 10.1111/j.1476-5381.1989.tb11833.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Rossitch E., Jr, Alexander E., 3rd, Black P. M., Cooke J. P. L-arginine normalizes endothelial function in cerebral vessels from hypercholesterolemic rabbits. J Clin Invest. 1991 Apr;87(4):1295–1299. doi: 10.1172/JCI115132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Vane J. R., Anggård E. E., Botting R. M. Regulatory functions of the vascular endothelium. N Engl J Med. 1990 Jul 5;323(1):27–36. doi: 10.1056/NEJM199007053230106. [DOI] [PubMed] [Google Scholar]
  21. Warren J. B., Maltby N. H., MacCormack D., Barnes P. J. Pulmonary endothelium-derived relaxing factor is impaired in hypoxia. Clin Sci (Lond) 1989 Dec;77(6):671–676. doi: 10.1042/cs0770671. [DOI] [PubMed] [Google Scholar]

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

RESOURCES