Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Hypertension in mice lacking the gene for endothelial nitric oxide synthase

Abstract

NITRIC oxide (NO), a potent vasodilator produced by endothelial cells, is thought to be the endothelium-dependent relaxing factor (EDRF) which mediates vascular relaxation in response to acetylcholine, bradykinin and substance P in many vascular beds1-6. NO has been implicated in the regulation of blood pressure and regional blood flow4-6, and also affects vascular smooth-muscle prolifera-tion and inhibits platelet aggregation and leukocyte adhesion. Abnormalities in endothelial production of NO occur in atherosclerosis, diabetes and hypertension7. Pharmacological blockade of NO production with arginine analogues such as i -nitroarginine (L-NA) or L-N-arginine methyl ester affects multiple isoforms of nitric oxide synthase (NOS), and so cannot distinguish their physiological roles8,9. To study the role of endothelial NOS (eNOS) in vascular function, we disrupted the gene encoding eNOS in mice. Endothelium-derived relaxing factor activity, as assayed by acetylcholine-induced relaxation, is absent, and the eNOS mutant mice are hypertensive. Thus eNOS mediates basal vasodilation. Responses to NOS blockade in the mutant mice suggest that non-endothelial isoforms of NOS may be involved in maintaining blood pressure.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

Peter Libby, Julie E. Buring, … Eldrin F. Lewis

References

  1. Palmer, R. M., Ferrige, A. G. & Moncada, S. Nature 327, 524–526 (1987).

    Article  ADS  CAS  Google Scholar 

  2. Snyder, S. H. Nature 372, 504–505 (1994).

    Article  ADS  CAS  Google Scholar 

  3. Bredt, D. S. & Snyder, S. H. A. Rev. Biochem. 63, 175–195 (1994).

    Article  CAS  Google Scholar 

  4. Furchgott, R. F. in Mechanisms of Vasodilatation (ed. Vanhoutte, P. M.) 401–414 (Raven, New York. 1988).

    Google Scholar 

  5. Ignarro, L. J., Buga, G. M., Wood, K. S., Byrnes, R. E. & Chaudhuri, G. Proc. natn. Acad. Sci. U.S.A. 84, 9265–9269 (1987).

    Article  ADS  CAS  Google Scholar 

  6. Rees, D. D., Palmer, R. M. & Mocada, S. Proc. natn. Acad. Sci. U.S.A. 86, 3375–3378 (1989).

    Article  ADS  CAS  Google Scholar 

  7. Moncada, S. & Higgs, A. New Engl. J. Med. 329, 2002–2012 (1993).

    Article  CAS  Google Scholar 

  8. Rees, D. D., Palmer, R. M., Schultz, R., Hodson, H. F. & Moncada, S. Br. J. Pharmac. 101, 746–752 (1990).

    Article  CAS  Google Scholar 

  9. Marletta, M. A. Cell 78, 927–930 (1994).

    Article  CAS  Google Scholar 

  10. Hevel, J. M. & Marletta, M. A. Methods Enzym. 233, 250–258 (1994).

    Article  CAS  Google Scholar 

  11. Forstermann, U., Pollack, J. S., Tracey, W. R. & Nakane, M. Meth. Enzym. 233, 258–264 (1994).

    Article  CAS  Google Scholar 

  12. Huang, P. L., Dawson, T. M., Bredt, D., Snyder, S. H. & Fishman, M. C. Cell 75, 1273–1286 (1993).

    Article  CAS  Google Scholar 

  13. Irikura, K. et al. Proc. natn. Acad. Sci. U.S.A. 92, 6823–6827 (1995).

    Article  ADS  CAS  Google Scholar 

  14. Sakuma, I. et al. Circulation Res. 70, 607–611 (1992).

    Article  CAS  Google Scholar 

  15. Vincent, S. R. & Kimura, H. Neuroscience 46, 755–783 (1992).

    Article  CAS  Google Scholar 

  16. Iadecola, C., Faris, P. L., Hartman, B. K. & Xu, X. Brain Res. 603, 173–179 (1993).

    Article  CAS  Google Scholar 

  17. Anderson, C. R. Neurosci. Lett. 139, 280–284 (1992).

    Article  CAS  Google Scholar 

  18. Toda, N., Ayajiki, K. & Okamura, T. J. vasc. Res. 30, 61–67 (1993).

    Article  CAS  Google Scholar 

  19. Ayajiki, K., Okamura, T. & Toda, N. Neuroscience 54, 819–825 (1993).

    Article  CAS  Google Scholar 

  20. Togashi, H. et al. J. Pharmac. exp. Ther. 262, 343–347 (1992).

    CAS  Google Scholar 

  21. Huang, Z. et al. Science 265, 1883–1885 (1994).

    Article  ADS  CAS  Google Scholar 

  22. Frey, C. et al. J, biol. Chem. 269, 26083–26091 (1994).

    CAS  Google Scholar 

  23. Gardiner, S. M., Kemp, P. A., Bennett, T., Palmer, R. M. & Moncada, S. Eur. J. Pharmac. 213, 449–451 (1992).

    Article  CAS  Google Scholar 

  24. Peart, W. S. in Hypertension 2nd edn (ed. Genest, J., Kuchel, O., Hamet, P. & Cantin, M.) (McGraw-Hall, New York, 1983).

    Google Scholar 

  25. Scrogin, K. E., Veelken, R. & Luft F. C. Hypertension 23, (2) 982–986 (1994).

    Article  CAS  Google Scholar 

  26. Matsuda, T., Bates, J. N., Lewis, S. J., Abboud, F. M. & Chapleau, M. W. Circulation Res. 76, 426–433 (1995).

    Article  CAS  Google Scholar 

  27. Da Silva, S. V., Da Silva, V. J., Ballejo, G., Salgado, M. C. O. & Slagado, H. C. Hypertension 23 (suppl.) 60–63 (1994).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huang, P., Huang, Z., Mashimo, H. et al. Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature 377, 239–242 (1995). https://doi.org/10.1038/377239a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/377239a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing