Genetic determinants of diastolic and pulse pressure map to different loci in Lyon hypertensive rats (original) (raw)

Nature Genetics volume 3, pages 354–357 (1993)Cite this article

Abstract

Several genetic loci involved in blood pressure regulation have recently been localized in experimental models of hypertension, but the manner in which they influence blood pressure remains unknown. Here, we report a study of the Lyon hypertensive rat strain showing that different loci are involved in the regulation of steady-state (diastolic pressure) and pulsatile (systolic – diastolic, or pulse pressure) components of blood pressure. Significant linkage was established between diastolic blood pressure and a microsatellite marker of the renin gene (REN) on rat chromosome 13, and between pulse pressure and the carboxypeptidase B gene (CPB) on chromosome 2. These findings show that two independent loci influence different haemodynamic components of blood pressure, and that pulse pressure has a specific genetic determination.

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

Access options

Subscribe to this journal

Receive 12 print issues and online access

$209.00 per year

only $17.42 per issue

Buy this article

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

Additional access options:

Similar content being viewed by others

References

  1. Ward, R. in Hypertension: Pathophysiology, diagnosis and management (eds Laragh, J.H. & Brenner, B.M.) 81–100 (Raven Press, New York, 1990).
    Google Scholar
  2. Rapp, J.P., Wang, S.M. & Dene, H. A genetic polymorphism in the renin gene of Dahl rats cosegregates with blood pressure. Science 243, 542–544 (1989).
    Article CAS PubMed Google Scholar
  3. Kurtz, T.W. et al. Cosegregation of the renin allele of the spontaneously hypertensive rat with an increase in blood pressure. J. Clin. Invest. 85, 1328–1332 (1990).
    Article CAS PubMed PubMed Central Google Scholar
  4. Pravnec, M. et al. The rat renin gene: Assignment to chromosome 13 and linkage to the regulation of blood pressure. Genomics 9, 466–472 (1991).
    Article Google Scholar
  5. Hilbert, P. et al. Chromosomal mapping of two genetic loci associated with blood-pressure regulation in hereditary hypertensive rats. Nature 353, 521–529 (1991).
    Article CAS PubMed Google Scholar
  6. Jacob, H. et al. Genetic mapping of a gene causing hypertension in the stroke-prone spontaneously hypertensive rat. Cell 67, 213–224 (1991).
    Article CAS PubMed Google Scholar
  7. Deng, Y. & Rapp, J. Cosegregation of blood pressure with angiotensin converting enzyme and atrial natriuretic peptide receptor genes using Dahl salt-sensitive rats. Nature Genet. 1, 267–272 (1992).
    Article CAS PubMed Google Scholar
  8. Canessa, M. et al. Increased sodium-lithium countertransport in red cells of patients with essential hypertension. New Engl. J. Med. 302, 772–776 (1980).
    Article CAS PubMed Google Scholar
  9. Hollenberg, N.K. et al. Abnormal renal sodium handling in essential hypertension: relation to failure of renal and adrenal modulation of response to angiotensin II. Am. J. Med. 81, 412–418 (1986).
    Article CAS PubMed Google Scholar
  10. Zinner, S.H. et al. Familial aggregation of urinary kallikrein concentration in childhood: relation to blood pressure, race and urinary electrolytes. Am. J. Epidemiol. 104, 124–132 (1976).
    Article CAS PubMed Google Scholar
  11. Soubrier, F. et al. in Genetic approaches to coronary heart disease and hypertension (eds. Berg, K. et al.) 27–37 (Springer-Verlag, Berlin, 1991).
    Book Google Scholar
  12. Vincent, M., Dupont, J. & Sassard, J. Simultaneous selection of spontaneously hypertensive, normotensive and lowtensive rats. Jap. Heart. J. 20(S1), 135–137 (1979).
    Google Scholar
  13. Serikawa et al. Rat gene mapping using PCR-analyzed microsatellites. Genetics 131, 703–723 (1992).
    Google Scholar
  14. Adams, M. et al. Enzyme markers in inbred rat strains: genetics of new markers and strain profiles. Biochem. Genet. 22, 611–629 (1984).
    Article CAS PubMed Google Scholar
  15. Safar, M.E. Pulse pressure in essential hypertension: clinical and therapeutical implications. J. Hyperten. 7, 769–776 (1989).
    Article CAS Google Scholar
  16. Laragh, J.H. et al. The vasoconstriction-volume spectrum in normotension and in the pathogenesis of hypertension. Fed. Proc. 41, 2415–2423 (1982).
    CAS PubMed Google Scholar
  17. Hall, J.E. et al. Blood pressure and renal function during chronic changes in sodium intake. Role of angiotensin. Am. J. Physiol. 239, F271–F280 (1980).
    CAS PubMed Google Scholar
  18. Nicols, W.W., O'Rourke, M.F. McDonald's Blood Flow in Arteries. Theoretical, experimental and clinical principles 216–250 (Lea and Febiger, Philadelphia, 1990).
    Google Scholar
  19. Lindpaintner, K., Takahashi, S. & Ganten, D. J Structural alterations of the renin gene in stroke-prone spontaneously hypertensive rats: Examination of genotype-phenotype correlations. Hypertension 8, 763–777 (1991).
    Article Google Scholar
  20. Su, D.F. et al. Blood pressure and baroreflex sensitivity in conscious hypertensive rats of Lyon strain. Am. J. Physiol. 251, H1111–1117 (1986).
    CAS PubMed Google Scholar
  21. Gustin, M.P., Cerutti, C. & Paultre, C.Z. Heterogeneous computer network for real-time haemodynamics signals processing. Comput. Biol. Med. 20, 205–15 (1990).
    Article CAS PubMed Google Scholar
  22. Lathrop, G.M. & Lalouel, J.M. Simple calculation of lod-scores on small computers. Am. J. hum. Genet. 36, 460–465 (1984).
    CAS PubMed PubMed Central Google Scholar
  23. Dixon, W.J. et al. BMDP Statistical Software Manual (University of California Press, Berkely, 1988).
    Google Scholar

Download references

Author information

Authors and Affiliations

  1. INSERM U. 358, Centre d'Etude du Polymorphisme Humain, 75010, Paris, France
    Christopher Dubay, Pascale Hilbert, Jean-Paul Beressi, Jacques S. Beckmann & G. Mark Lathrop
  2. URA CNRS 1483, Département de Physiologie et de la Pharmacologie Clinique, Faculté de Pharmacie, 8 avenue Rockefeller, 69373, Lyon, France
    Madeleine Vincent & Jean Sassard
  3. Department of Medicine, University of Leicester, Leicester Royal Infirmary, PO Box 65, Leicester, LE27LX, UK
    Nilesh J. Samani & Michael A. Kaiser
  4. IRIBNH, Campuse Erasme, Brussels, 1070, Belgium
    Pascale Hilbert
  5. INSERM U. 36, Collège de France, 3 rue d'Ulm, 75005, Paris, France
    Yuri Kotelevtsev & Florent Soubrier

Authors

  1. Christopher Dubay
    You can also search for this author inPubMed Google Scholar
  2. Madeleine Vincent
    You can also search for this author inPubMed Google Scholar
  3. Nilesh J. Samani
    You can also search for this author inPubMed Google Scholar
  4. Pascale Hilbert
    You can also search for this author inPubMed Google Scholar
  5. Michael A. Kaiser
    You can also search for this author inPubMed Google Scholar
  6. Jean-Paul Beressi
    You can also search for this author inPubMed Google Scholar
  7. Yuri Kotelevtsev
    You can also search for this author inPubMed Google Scholar
  8. Jacques S. Beckmann
    You can also search for this author inPubMed Google Scholar
  9. Florent Soubrier
    You can also search for this author inPubMed Google Scholar
  10. Jean Sassard
    You can also search for this author inPubMed Google Scholar
  11. G. Mark Lathrop
    You can also search for this author inPubMed Google Scholar

Rights and permissions

About this article

Cite this article

Dubay, C., Vincent, M., Samani, N. et al. Genetic determinants of diastolic and pulse pressure map to different loci in Lyon hypertensive rats.Nat Genet 3, 354–357 (1993). https://doi.org/10.1038/ng0493-354

Download citation

This article is cited by