Skip to main content
SpringerLink
Log in

Endothelium-Derived Vasodilators

  • Chapter
Vascular Endothelium

  • 94 Accesses

Abstract

The importance of the endothelium in vessel wall homeostasis has recently become apparent. The vascular endothelium has been discovered to generate two potent vasodilators, prostacyclin (Moncada et al., 1976) and endothelium-derived relaxing factor (EDRF; Furchgott and Zawadzki, 1980) in response to a number of chemical or mechanical stimuli. Prostacyclin is the most potent inhibitor of platelet aggregation yet discovered (for review see Moncada, 1982). EDRF is an inhibitor of both platelet aggregation (Radomski et al., 1987a) and adhesion (Radomski et al., 1987b).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Amezcua, J.L., Dusting, G.J., Palmer, R.M.J. and Moncada, S. Acetylcholine induces vasodilatation in the rabbit isolated heart through the release of nitric oxide, the endogenous nitrovasodilator. Br. J. Pharmacol. 95:830–834, 1988.

    Article  PubMed  CAS  Google Scholar 

  • Blair, I.A., Barrow, S.E., Waddell, K.A., Lewis, P.J. and Dollery, C.T. Prostacyclin is not a circulating hormone in man. Prostaglandins. 23: 579–589, 1982.

    Article  PubMed  CAS  Google Scholar 

  • Blough, N.V. and Zafiriou, O.C. Reaction of superoxide with nitric oxide to form peroxonitrite in alkaline aqueous solution. Inorg. Chem. 24:3502–3504, 1985.

    Article  CAS  Google Scholar 

  • Busse, R. Stimulation of soluble guanylate cyclase activity by endothelium-derived relaxant factor: a general principle of its vasodilator and anti-aggregatory properties. Thromb. Res. Suppl. VII, p. 3, 1987.

    Google Scholar 

  • Chen, W-Z., Palmer, R.M.J. and Moncada, S. The release of nitric oxide from the rabbit aorta. J. Vasc. Med Biol. In press, 1989.

    Google Scholar 

  • Dale, H.H. Progress in autopharmacology. A survey of present knowledge of the chemical regulation of certain functions by natural constituents of the tissues. Bull Johns Hopk. Hosp. 53:297–347, 1933

    CAS  Google Scholar 

  • Furchgott, R.F. The role of endothelium in the responses of vascular smooth muscle to drugs. Ann. Rev Pharmacol. Toxicol. 24:175–197, 1984.

    Article  CAS  Google Scholar 

  • Furchgott, R.F. Studies on relaxation of rabbit aorta by sodium nitrite: the basis for the proposal that the acid-activatable inhibitory factor from bovine retractor penis is inorganic nitrite and the endothelium-derived relaxing factor is nitric oxide. In: Mechanisms of Vasodilatation, ed. by Vanhoutte, P.M. Raven Press, New York. Vol. IV:401–414, 1988.

    Google Scholar 

  • Furchgott, R.F. and Zawadzki, J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 288:373–376, 1980.

    Article  PubMed  CAS  Google Scholar 

  • Gruetter, C.A., Gruetter, D.Y., Lyon, J.E., Kadowitz, P.J. and Ignarro, L.J. Relationship between cyclic guanosine 3′:5′-monophosphate formation and relaxation of coronary arterial smooth muscle by glyceryl trinitrate, nitroprusside, nitrite and nitric oxide: effects of methylene blue and methylhemoglobin. J. Pharmacol Exp. Ther. 219:181–186, 1981.

    PubMed  CAS  Google Scholar 

  • Gryglewski, R.J., Palmer, R.M.J. and Moncada, S. Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature. 320: 454–456, 1986.

    Article  PubMed  CAS  Google Scholar 

  • Hibbs, J.B. Jr., Vavrin, Z. and Taintor, R.R. L-arginine is required for expression of the activated macrophage effector mechanism causing selective metabolic inhibition in target cells. J. Immunol. 138:550–565, 1987a.

    PubMed  CAS  Google Scholar 

  • Hibbs, J.B. Jr., Taintor, R.R. and Vavrin, Z. Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite. Science. 235:473–476, 1987b.

    Article  PubMed  CAS  Google Scholar 

  • Hutchinson, P.J.A., Palmer, R.M.J. and Moncada, S. Comparative pharmacology of EDRF and nitric oxide on vascular strips. Eur. J. Pharmacol. 141:445–451, 1987.

    Article  PubMed  CAS  Google Scholar 

  • Ignarro, L.J. and Kadowitz, P.J. Pharmacological and physiological role of cyclic GMP in vascular smooth muscle relaxation. Ann. Rev. Pharmacol. Toxicol. 25:171–191, 1985.

    Article  CAS  Google Scholar 

  • Ignarro, L.J., Byrns, R.E. and Wood K.S. Biochemical and pharmacological properties of Endothelium-Derived Relaxing Factor and its similarity to nitric oxide radical. In: Mechanisms of Vasodilatation. ed. by Vanhoutte P.M. Raven Press, New York. Vol. IV:427–436, 1988.

    Google Scholar 

  • Kukovetz, W.R., Holzmann, S. and Poch, G. Function of cyclic GMP in acetylcholine-induced contraction of coronary smooth muscle. Naunyn-Schmiedeberg’s Arch. Pharmacol. 319:29–33, 1982.

    Article  CAS  Google Scholar 

  • Macdonald, P.S., Read, M.A. and Dusting, G.J. Synergistic inhibition of platelet aggregation by endothelium-derived relaxing factor and prostacyclin. Thromb. Res. 49:437–449, 1988.

    Article  PubMed  CAS  Google Scholar 

  • Martin, W., Villani, G.M., Jothianandan, D. and Furchgott, R.F. Selective blockade of endothelium-dependent and glyceryl trinitrate-induced relaxation by hemoglobin and by methylene blue in the rabbit aorta. J. Pharmacol. Exp. Ther. 232:708–716, 1985a.

    PubMed  CAS  Google Scholar 

  • Martin, W., Villani, G.M., Jothianandan, D. and Furchgott, R.F. Blockade of endothelium-dependent and glyceryl trinitrate-induced relaxation of rabbit aorta by certain ferrous haemoproteins. J. Pharmacol. Exp. Ther. 233:679–685, 1985b.

    PubMed  CAS  Google Scholar 

  • Martin, W., Furchgott, R.F., Villani, G.M. and Jothianandan, D. Phosphodiesterase inhibitors induce endothelium-dependent relaxation of rat and rabbit aorta by potentiating the effects of spontaneously released endothelium-derived relaxing factor. J. Pharmacol. Exp. Ther. 237:539–547, 1986a.

    PubMed  CAS  Google Scholar 

  • Martin, W., Smith, J.A. and White, D.G. The mechanisms by which haemoglobin inhibits the relaxation of rabbit aorta induced by nitrovasodilators, nitric oxide or bovine retractor penis inhibitory factor. Br. J. Pharmacol. 89:562–571, 1986b.

    Google Scholar 

  • Moncada, S. Biological importance of prostacyclin. Br. J. Pharmacol. 76:3–31, 1982.

    Article  PubMed  CAS  Google Scholar 

  • Moncada, S., Gryglewski, R., Bunting, S. and Vane, J.R. An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature. 263:663–665, 1976.

    Article  PubMed  CAS  Google Scholar 

  • Moncada, S., Palmer, R.M.J. and Gryglewski, R.J. Mechanism of action of some inhibitors of endothelium-derived relaxing factor. Proc. Natl. Acad. Sci. USA. 83:9164–9168, 1986.

    Article  PubMed  CAS  Google Scholar 

  • Moncada, S., Palmer, R.M.J. and Higgs, E.A. Prostacyclin and endothelium-derived relaxing factor: biological interactions and significance. In: Thrombosis and Haemostasis Verstraete, M., Vermylen, J., Lijnen, H.R., Arnout, J. ed. by Leuven University Press, pp. 587–618, 1987.

    Google Scholar 

  • Moncada, S., Palmer, R.M.J. and Higgs, E.A. Discovery of nitric oxide as the endogenous nitrovasodilator. Hypertension. 12:365–372, 1988.

    Article  PubMed  CAS  Google Scholar 

  • Nakashima, S., Tohmatsu, T., Hattori, H., Okano, Y. and Nozawa, Y. Inhibitory action of cyclic GMP on secretion, polyphosphoinositide hydrolysis and calcium mobilization in thrombin-stimulated human platelets. Biochem. Biophys. Res. Commun. 135:1099–1104, 1986.

    Article  PubMed  CAS  Google Scholar 

  • Palmer, R.M.J., Ferrige, A.G. and Moncada, S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 327:524–526, 1987.

    Article  PubMed  CAS  Google Scholar 

  • Palmer, R.M.J., Ashton, D.S. and Moncada, S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature. 333:664–666, 1988a.

    Article  PubMed  CAS  Google Scholar 

  • Palmer, R.M.J., Rees, D.D., Ashton, D.S. and Moncada, S. L-arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation. Biochem. Biophys. Res. Commun. 153:1251–1256, 1988b.

    Article  PubMed  CAS  Google Scholar 

  • Radomski, M.W., Palmer, R.M.J. and Moncada, S. Comparative pharmacology of endothelium-derived relaxing factor, nitric oxide and prostacyclin in platelets. Br. J. Pharmacol. 92:181–187, 1987a.

    Article  PubMed  CAS  Google Scholar 

  • Radomski, M.W., Palmer, R.M.J. and Moncada, S. The role of nitric oxide and cGMP in platelet adhesion to vascular endothelium. Biochem. Biophys. Res. Commun. 148:1482–1489, 1987b.

    Article  PubMed  CAS  Google Scholar 

  • Radomski, M.W., Palmer, R.M.J. and Moncada, S. The anti-aggregating properties of vascular endothelium: interactions between prostacyclin and nitric oxide. Br. J. Pharmacol. 92:639–646, 1987c.

    Article  PubMed  CAS  Google Scholar 

  • Radomski, M.W., Palmer, R.M.J. and Moncada, S. Endogenous nitric oxide inhibits human platelet adhesion to vascular endothelium. Lancet. ii: 1057–1058, 1987d.

    Article  Google Scholar 

  • Radomski, M.W., Palmer, R.M.J., Read, N.G. and Moncada, S. Isolation and washing of human platelets with nitric oxide. Thromb. Res. 50:537–546, 1988.

    Article  PubMed  CAS  Google Scholar 

  • Rapoport, R.M. and Murad, F. Agonist induced endothelium-dependent relaxation in rat thoracic aorta may be mediated through cyclic GMP. Circ. Res. 52:352–357, 1983.

    Article  PubMed  CAS  Google Scholar 

  • Rees, D.D., Palmer, R.M.J., Hodson, H.F. and Moncada, S. A specific inhibitor of nitric oxide formation from L-arginine attenuates endothelium-dependent relaxation. Br. J. Pharmacol. In press, 1989.

    Google Scholar 

  • Rimele, T.J., Sturm, R.J., Adams, L.M., Henry, D.E., Heaslip, R.J., Weichman, B.M. and Grimes, D. Interaction of neutrophils with vascular smooth muscle: identification of a neutrophil-derived relaxing factor. J. Pharm. Exp. Ther. 245:102–111, 1988.

    CAS  Google Scholar 

  • Rubanyi, G.M. and Vanhoutte, P.M. Superoxide anions and hyperoxia inactivate endothelium-derived relaxing factor. Am. J. Physiol. 250:H222–H227, 1986.

    Google Scholar 

  • Sneddon, J.M. and Vane, J.R. Endothelium-derived relaxing factor reduces platelet adhesion to bovine endothelial cells. Proc. Natl. Acad. Sci. USA. 85:2800–2804, 1988.

    Article  PubMed  CAS  Google Scholar 

  • Stuehr, D.J. and Marietta, M.A. Mammalian nitrate biosynthesis: mouse macrophages produce nitrite and nitrate in response to Escherichia coli lipopolysaccharide. Proc. Natl. Acad Sci. USA. 82:7738–7742, 1985.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Wellcome Research Laboratories, Langley Court, Beckenham Kent, UK

    S. Moncada, R. M. J. Palmer & E. A. Higgs

Authors
  1. S. Moncada
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. M. J. Palmer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. A. Higgs
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Medical College of Georgia, Augusta, Georgia, USA

    John D. Catravas

  2. Yale University School of Medicine, New Haven, Connecticut, USA

    C. Norman Gillis

  3. University of Miami School of Medicine, Miami, Florida, USA

    Una S. Ryan

Rights and permissions

Reprints and permissions

Copyright information

© 1989 Plenum Press, New York

About this chapter

Cite this chapter

Moncada, S., Palmer, R.M.J., Higgs, E.A. (1989). Endothelium-Derived Vasodilators. In: Catravas, J.D., Gillis, C.N., Ryan, U.S. (eds) Vascular Endothelium. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-8532-5_22

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-8532-5_22

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-8534-9

  • Online ISBN: 978-1-4684-8532-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation