, Volume 168, Supplement 1, pp 35–42 | Cite as

Endothelium-derived relaxing factors and the human pulmonary circulation

  • D. McCormack
Endothelium- And Epithelium-Derived Relaxing And Contracting Factors


The vasodilator effect of acetylcholine on the pulmonary circulation was first described over 30 years ago, however, the mechanism remained unknown until Furchgott described the endothelium-dependent relaxation of certain vasodilators. It was not until 1987 that endothelium-derived relaxant factor (EDRF) was demonstrated to dilate human pulmonary arteries in vitro. Despite this work, the physiologic role of EDRF in the pulmonary circulation is not known. It has been suggested that hypoxia-induced inhibition of EDRF action or release from pulmonary artery endothelial cells may have a role in hypoxic pulmonary vasoconstriction (HPV) but present evidence suggests that loss of EDRF activity is not directly involved in the phenomenon of HPV. It is more likely that EDRF is released from pulmonary artery endothelial cells during hypoxia and this released EDRF then modulates HPV. If EDRF does modulate HPV in vivo then the role of EDRF in the altered HPV found in disease merits attention. It is known that in disease states such as acute lung injury and pneumonia there is loss or attenuation of HPV which inevitably leads to increased V/Q mismatch and hypoxemia. Whether this attenuation of HPV is due to release of an endogenous vasodilator such as EDRF is presently being investigated. Additionally, there is in vitro evidence that loss of EDRF activity may be important in the genesis of pulmonary hypertension such as found in severe cystic fibrosis. During the next decade the role of EDRF in the human pulmonary circulation in both health and disease will undoubtedly be elucidated.

Key words

Pulmonary artery Endothelium-derived relevant factor Hypoxic pulmonary vasoconstriction Pulmonary hypertension 


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  1. 1.
    Fritts HW Jr., Harris P, Clauss RH, Odell JE, Cournand A (1958) The effect of acetylcholine on the human pulmonary circulation under normal and hypoxic conditions. J Clin Invest 37(1):99–110PubMedCrossRefGoogle Scholar
  2. 2.
    Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373–376PubMedCrossRefGoogle Scholar
  3. 3.
    McCormack DG, MAk JC, Minnette P, Barnes PJ (1989) Muscarinic receptor subtypes mediating vasodilation in the pulmonary artery. Eur J Pharmacol 158:293–297CrossRefGoogle Scholar
  4. 4.
    Greenberg B, Rhoden K, Barnes PJ (1987) Endothelium-dependent relaxation of human pulmonary arteries. Am J Physiol 252 (Heart Circ Physiol 21):H434–438PubMedGoogle Scholar
  5. 5.
    Weir EK (1978) Does normoxic pulmonary vasodilatation rather than hypoxic vasoconstriction account for the pulmonary pressor response to hypoxia? Lancet 8062:476–477CrossRefGoogle Scholar
  6. 6.
    Griffith TM, Edwards DH, Collins P, Lewis MJ, Henderson AH (1985) Endothelium derived relaxant factor. J R Coll Phys Lond 19(2):74–79Google Scholar
  7. 7.
    Collins P, Chappell SP, Griffith TM, Lewis MJ, Henderson AH (1986) Differences in basal endothelium-derived relaxing factor activity in different artery types. J Cardiovasc Pharmacol 8:1158–1162PubMedCrossRefGoogle Scholar
  8. 8.
    Yamaguchi T, Rodman D, O’Brien R, McMurtry I (1989) Modulation of pulmonary artery contraction by endothelium-derived relaxing factor. Eur J Pharmacol 161:259–262PubMedCrossRefGoogle Scholar
  9. 9.
    Rodman D, Yamaguchi T, O’Brien R, McMurtry I (1988) Methylene blue enhances hypoxic contraction in isolated rat pulmonary arteries. Chest 93(3):93S-94SPubMedCrossRefGoogle Scholar
  10. 10.
    Brashers VL, Peach MJ, Rose CE Jr. (1988) Augmentation of hypoxic pulmonary vasocon-striction in the isolated perfused rat lung by in vitro antagonists of endothelium-dependent relaxation. J Clin Invest 82:1495–1502PubMedCrossRefGoogle Scholar
  11. 11.
    Mazmanian GM, Baudet B, Brink C, Cerrina J, Kirkiacharian S, Weiss M (1989) Methylene blue potentiates vascular reactivity in isolated rat lungs. J Appl Physiol 66(3):1040–1045PubMedGoogle Scholar
  12. 12.
    Van de Voorde J, Leusen I (1986) Endothelium-dependent and independent relaxation of aortic rings from hypertensive rats. Am J Physiol 250 (Heart Circ Physiol 19):H711-H717PubMedGoogle Scholar
  13. 13.
    Mayhan WG, Faraci FM, Heistad DD (1987) Impairment of endothelium-dependent responses of cerebral arterioles in chronic hypertension. Am J Physiol 253 (Heart Circ Physiol 22):H1435-H1440PubMedGoogle Scholar
  14. 14.
    Dinh Xuan AT, Higenbottam TW, Pepke-Zaba J, Clelland C, Wallwork J (1989) Reduced endothelium-dependent relaxation of cystic fibrosis pulmonary arteries. Eur J Phamacol 163:401–403CrossRefGoogle Scholar
  15. 15.
    Rounds S, Farber HW, Hill NS, O’Brien RF (1985) Effects of endothelial cell injury on pulmonary vascular reactivity. Chest 88(4):213S-216SPubMedCrossRefGoogle Scholar
  16. 16.
    Graham LM, Vasil ML, Voelkel NF, Stenmark KR (1989) Chronic pseudomonas pneumonia results in reduced pulmonary vasoreactivity and elevated pulmonary artery pressure. Am Rev Respir Dis A71Google Scholar

Copyright information

© Springer-Verlag New York, Inc. 1990

Authors and Affiliations

  • D. McCormack
    • 1
  1. 1.Victoria HospitalLondonCanada

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