Skip to main content
NCBI home page
Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 1995 Jun;48(6):519–524. doi: 10.1136/jcp.48.6.519

Circulating endothelin-1 concentrations in patients with chronic hypoxia.

C Ferri 1, C Bellini 1, C De Angelis 1, L De Siati 1, A Perrone 1, G Properzi 1, A Santucci 1
PMCID: PMC502680  PMID: 7665694

Abstract

AIMS--To evaluate the behavior of plasma endothelin-1 in patients with chronic hypoxia. METHODS--Fifteen male patients (mean age 52.1 +/- 3.1 years) with mild chronic obstructive pulmonary disease (COPD) were studied. Twelve healthy men (mean age 48.3 +/- 5.4 years) served as controls. Both patients and controls underwent standard pulmonary function tests, echocardiographic evaluation, and arterial blood gas evaluation. Blood samples for endothelin-1 assay were taken from a previously incannulated antecubital vein after 60 minutes of rest in the supine position. Endothelin-1 was measured by radioimmunoassay after extraction from plasma. RESULTS--Patients with chronic hypoxia had lower PaO2 values (66.1 +/- 6.2 mmHg) than controls (83.8 +/- 2.7 mmHg) but PaCO2 values were similar (38.1 +/- 2.5 v 36.7 +/- 3.1 mmHg, respectively). Arterial pulmonary pressure, therefore, was higher in patients (18.1 +/- 3.7 mmHg) than in controls (10.4 +/- 2.7 mmHg) as were circulating endothelin-1 concentrations (1.22 +/- 0.36 v 0.57 +/- 0.1 pg/ml). Furthermore, plasma endothelin-1 concentrations were negatively correlated with PaO2 and directly correlated with pulmonary pressure levels. No significant correlations were found in controls. CONCLUSIONS--These results show a clear relation between chronic hypoxia and circulating endothelin-1 concentrations. Therefore, chronic hypoxia may be regarded as an important stimulus for endothelin-1 release and as one of the main contributors to increased vasoconstriction in the vascular pulmonary bed which often accompanies lung disease.

Full text

PDF
519

Selected References

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

  1. 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]
  2. Bowen-Pope D. F., Hart C. E., Seifert R. A. Sera and conditioned media contain different isoforms of platelet-derived growth factor (PDGF) which bind to different classes of PDGF receptor. J Biol Chem. 1989 Feb 15;264(5):2502–2508. [PubMed] [Google Scholar]
  3. Davies P., Maddalo F., Reid L. Effects of chronic hypoxia on structure and reactivity of rat lung microvessels. J Appl Physiol (1985) 1985 Mar;58(3):795–801. doi: 10.1152/jappl.1985.58.3.795. [DOI] [PubMed] [Google Scholar]
  4. De Angelis C., Farrace S., Urbani L., Porcú S., Ferri C., D'Amelio R., Santucci A., Balsano F. Effects of high altitude exposure on plasma and urinary digoxin-like immunoreactive substance. Am J Hypertens. 1992 Sep;5(9):600–607. doi: 10.1093/ajh/5.9.600. [DOI] [PubMed] [Google Scholar]
  5. Deleuze P. H., Adnot S., Shiiya N., Roudot Thoraval F., Eddahibi S., Braquet P., Chabrier P. E., Loisance D. Y. Endothelin dilates bovine pulmonary circulation and reverses hypoxic pulmonary vasoconstriction. J Cardiovasc Pharmacol. 1992 Mar;19(3):354–360. doi: 10.1097/00005344-199203000-00008. [DOI] [PubMed] [Google Scholar]
  6. Giaid A., Yanagisawa M., Langleben D., Michel R. P., Levy R., Shennib H., Kimura S., Masaki T., Duguid W. P., Stewart D. J. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med. 1993 Jun 17;328(24):1732–1739. doi: 10.1056/NEJM199306173282402. [DOI] [PubMed] [Google Scholar]
  7. Hatle L., Brubakk A., Tromsdal A., Angelsen B. Noninvasive assessment of pressure drop in mitral stenosis by Doppler ultrasound. Br Heart J. 1978 Feb;40(2):131–140. doi: 10.1136/hrt.40.2.131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hay D. W. Pharmacological evidence for distinct endothelin receptors in guinea-pig bronchus and aorta. Br J Pharmacol. 1992 Aug;106(4):759–761. doi: 10.1111/j.1476-5381.1992.tb14407.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Holden W. E., McCall E. Hypoxia-induced contractions of porcine pulmonary artery strips depend on intact endothelium. Exp Lung Res. 1984;7(2):101–112. doi: 10.3109/01902148409069671. [DOI] [PubMed] [Google Scholar]
  10. Kourembanas S., Marsden P. A., McQuillan L. P., Faller D. V. Hypoxia induces endothelin gene expression and secretion in cultured human endothelium. J Clin Invest. 1991 Sep;88(3):1054–1057. doi: 10.1172/JCI115367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lüscher T. F., Boulanger C. M., Dohi Y., Yang Z. H. Endothelium-derived contracting factors. Hypertension. 1992 Feb;19(2):117–130. doi: 10.1161/01.hyp.19.2.117. [DOI] [PubMed] [Google Scholar]
  12. Marsden P. A., Brenner B. M. Nitric oxide and endothelins: novel autocrine/paracrine regulators of the circulation. Semin Nephrol. 1991 Mar;11(2):169–185. [PubMed] [Google Scholar]
  13. Miyauchi T., Yanagisawa M., Tomizawa T., Sugishita Y., Suzuki N., Fujino M., Ajisaka R., Goto K., Masaki T. Increased plasma concentrations of endothelin-1 and big endothelin-1 in acute myocardial infarction. Lancet. 1989 Jul 1;2(8653):53–54. doi: 10.1016/s0140-6736(89)90303-6. [DOI] [PubMed] [Google Scholar]
  14. Rakugi H., Tabuchi Y., Nakamaru M., Nagano M., Higashimori K., Mikami H., Ogihara T., Suzuki N. Evidence for endothelin-1 release from resistance vessels of rats in response to hypoxia. Biochem Biophys Res Commun. 1990 Jun 29;169(3):973–977. doi: 10.1016/0006-291x(90)91989-6. [DOI] [PubMed] [Google Scholar]
  15. Rubanyi G. M., Botelho L. H. Endothelins. FASEB J. 1991 Sep;5(12):2713–2720. doi: 10.1096/fasebj.5.12.1916094. [DOI] [PubMed] [Google Scholar]
  16. Saijonmaa O., Ristimäki A., Fyhrquist F. Atrial natriuretic peptide, nitroglycerine, and nitroprusside reduce basal and stimulated endothelin production from cultured endothelial cells. Biochem Biophys Res Commun. 1990 Dec 14;173(2):514–520. doi: 10.1016/s0006-291x(05)80064-6. [DOI] [PubMed] [Google Scholar]
  17. Schini V. B., Hendrickson H., Heublein D. M., Burnett J. C., Jr, Vanhoutte P. M. Thrombin enhances the release of endothelin from cultured porcine aortic endothelial cells. Eur J Pharmacol. 1989 Jun 20;165(2-3):333–334. doi: 10.1016/0014-2999(89)90733-4. [DOI] [PubMed] [Google Scholar]
  18. Stewart D. J., Levy R. D., Cernacek P., Langleben D. Increased plasma endothelin-1 in pulmonary hypertension: marker or mediator of disease? Ann Intern Med. 1991 Mar 15;114(6):464–469. doi: 10.7326/0003-4819-114-6-464. [DOI] [PubMed] [Google Scholar]
  19. Takuwa N., Takuwa Y., Yanagisawa M., Yamashita K., Masaki T. A novel vasoactive peptide endothelin stimulates mitogenesis through inositol lipid turnover in Swiss 3T3 fibroblasts. J Biol Chem. 1989 May 15;264(14):7856–7861. [PubMed] [Google Scholar]
  20. Vender R. L., Clemmons D. R., Kwock L., Friedman M. Reduced oxygen tension induces pulmonary endothelium to release a pulmonary smooth muscle cell mitogen(s). Am Rev Respir Dis. 1987 Mar;135(3):622–627. doi: 10.1164/arrd.1987.135.3.622. [DOI] [PubMed] [Google Scholar]
  21. Wagner O. F., Christ G., Wojta J., Vierhapper H., Parzer S., Nowotny P. J., Schneider B., Waldhäusl W., Binder B. R. Polar secretion of endothelin-1 by cultured endothelial cells. J Biol Chem. 1992 Aug 15;267(23):16066–16068. [PubMed] [Google Scholar]
  22. Wagner O. F., Nowotny P., Vierhapper H., Waldhäusl W. Plasma concentrations of endothelin in man: arterio-venous differences and release during venous stasis. Eur J Clin Invest. 1990 Oct;20(5):502–505. doi: 10.1111/j.1365-2362.1990.tb01892.x. [DOI] [PubMed] [Google Scholar]
  23. Yoshizumi M., Kurihara H., Morita T., Yamashita T., Oh-hashi Y., Sugiyama T., Takaku F., Yanagisawa M., Masaki T., Yazaki Y. Interleukin 1 increases the production of endothelin-1 by cultured endothelial cells. Biochem Biophys Res Commun. 1990 Jan 15;166(1):324–329. doi: 10.1016/0006-291x(90)91948-r. [DOI] [PubMed] [Google Scholar]
  24. Yoshizumi M., Kurihara H., Sugiyama T., Takaku F., Yanagisawa M., Masaki T., Yazaki Y. Hemodynamic shear stress stimulates endothelin production by cultured endothelial cells. Biochem Biophys Res Commun. 1989 Jun 15;161(2):859–864. doi: 10.1016/0006-291x(89)92679-x. [DOI] [PubMed] [Google Scholar]
  25. de Nucci G., Thomas R., D'Orleans-Juste P., Antunes E., Walder C., Warner T. D., Vane J. R. Pressor effects of circulating endothelin are limited by its removal in the pulmonary circulation and by the release of prostacyclin and endothelium-derived relaxing factor. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9797–9800. doi: 10.1073/pnas.85.24.9797. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Pathology are provided here courtesy of BMJ Publishing Group

RESOURCES