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:

Behavioural and cardiovascular effects of disrupting the angiotensin II type-2 receptor gene in mice

A Correction to this article was published on 28 March 1996

Abstract

ANGIOTENSIN II, a potent regulator of blood pressure and of water and electrolyte balance, binds to two different G-protein-coupled receptors. The type-1 receptor (AT1,) mediates the vasopressive and aldosterone-secreting effects of angiotensin II, but the function of the type-2 receptor (AT2; refs 1, 2) is unknown, although it is expressed in both adult3 and embryonic4 life. To address this question, we have generated mice lacking the gene encoding the AT2 receptor. Mutant mice develop normally, but have an impaired drinking response to water deprivation as well as a reduction in spontaneous movements. Their baseline blood pressure is normal, but they show an increased vasopressor response to injection of angiotensin II. Thus, although the AT2 receptor is not required for embryonic development, it plays a role in the central nervous system and cardiovascular functions that are mediated by the renin-angiotensin system.

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

Access options

Buy this article

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

Similar content being viewed by others

References

  1. Kambayashi, Y. et al. J. biol. Chem. 268, 24543–24546 (1993).

    CAS  Google Scholar 

  2. Mukoyama, M. et al. J. biol. Chem. 268, 24539–24542 (1993).

    CAS  Google Scholar 

  3. Zhuo, et al. in Hypertension: Pathophysiology, Diagnosis, and Management (eds Laragh, J. H, & Brenner, B. M.) 1739–1762 (Raven, New York, 1995).

    Google Scholar 

  4. Grady, E. F., Sechi, L. A., Griffin, C. A., Schambelan, M. & Kalinyak, J. E. J. clin. Invest. 88, 921–933 (1991).

    Article  CAS  Google Scholar 

  5. Chassagne, C., Beatty, B. G. & Meloche, S. Genomics 25, 601–603 (1995).

    Article  CAS  Google Scholar 

  6. Koike, G. et al. Biochem. biophys. Res. Commun. 203, 1842–1850 (1994).

    Article  CAS  Google Scholar 

  7. Feuillan, P. P., Millan, M. A. & Aguilera, G. Regul. Pept. 44, 159–169 (1993).

    Article  CAS  Google Scholar 

  8. Wright, J. W. & Harding, J. W. Neurosci. Biobehav. Rev. 18, 21–53 (1994).

    Article  CAS  Google Scholar 

  9. Cooney, A. S. & Fitzsimons, J. T. Expl Physiol. 78, 767–774 (1993).

    Article  CAS  Google Scholar 

  10. Hogarty, D. C., Speakman, E. A., Puig, V. & Phillips, M. I. Brain Res. 586, 289–294 (1992).

    Article  CAS  Google Scholar 

  11. Rowland, N. E., Rozelle, A., Riley, P. J. & Fregly, M. J. Brain Res. Bull. 29, 389–393 (1992).

    Article  CAS  Google Scholar 

  12. Rowland, N. E. & Fregly, M. J. Brain Res. Bull. 32, 391–394 (1993).

    Article  CAS  Google Scholar 

  13. Dourish, C. T., Duggan, J. A. & Banks, R. J. Eur. J. Pharmac. 211, 113–116 (1992).

    Article  CAS  Google Scholar 

  14. Georgiev, V. Pol. J. Pharmac. Pharm. 42, 553–562 (1990).

    Article  CAS  Google Scholar 

  15. Georgiev, V., Getova, D. & Opitz, M. Meth. Find. Exp. Clin. Pharmac. 13, 5–9 (1991).

    CAS  Google Scholar 

  16. Petkova, B., Georgiev, V. & Kambourova, T. Acta Physiol. Pharmac. Bulg. 17, 84–90 (1991).

    CAS  Google Scholar 

  17. Rowe, B. P., Saylor, D. L. & Speth, R. C. Neuroendocrinology 55, 563–573 (1992).

    Article  CAS  Google Scholar 

  18. Tsutsumi, K. & Saavedra, J. M. Molec Pharmac. 41, 290–297 (1992).

    CAS  Google Scholar 

  19. Sumners, C. & Phillips, M. I. Am. J. Physiol. 244, R257–R263 (1983).

    CAS  PubMed  Google Scholar 

  20. Huang, Y., Rogers, J. & Henderson, G. J. Neurochem. 49, 1541–1549 (1987).

    Article  CAS  Google Scholar 

  21. Ichicki, T. et al. Nature 377, 748–750 (1995).

    Article  ADS  Google Scholar 

  22. Viswanathan, M., Stromberg, C., Seltzer, A. & Saavedra, J. M. J. clin. Invest. 90, 1707–1712 (1992).

    Article  CAS  Google Scholar 

  23. Lopez, J. J. et al. Am. J. Physiol. H844–H852 (1994).

  24. Nio, Y., Matsubara, H., Murasawa, S., Kanasaki, M. & Inada, M. J. clin. Invest. 95, 46–54 (1995).

    Article  CAS  Google Scholar 

  25. Grady, E. F. & Kalinyak, J. E. Regul. Pept. 44, 171–180 (1993).

    Article  CAS  Google Scholar 

  26. Nakajima, M., Mukoyama, M., Pratt, R. E., Horiuchi, M. & Dzau, V. J. Biochem. biophys. Res. Commun. 197, 393–399 (1993).

    Article  CAS  Google Scholar 

  27. Soriano, P., Montgomery, C., Geske, R. & Bradley, A. Cell 64, 693–702 (1991).

    Article  CAS  Google Scholar 

  28. Nagy, A., Rossant, J., Nagy, R., Abramow-Newerly, W. & Roder, J. C. Proc. natn. Acad. Sci. U.S.A. 90, 8424–8428 (1993).

    Article  ADS  CAS  Google Scholar 

  29. Wood, S. A., Allen, N. D., Rossant, J., Auerbach, A. & Nagy, A. Nature 365, 87–89 (1993).

    Article  ADS  CAS  Google Scholar 

  30. Xu, M. et al. Cell 79, 945–955 (1994).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hein, L., Barsh, G., Pratt, R. et al. Behavioural and cardiovascular effects of disrupting the angiotensin II type-2 receptor gene in mice. Nature 377, 744–747 (1995). https://doi.org/10.1038/377744a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/377744a0

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