Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1997 Feb 15;99(4):577–581. doi: 10.1172/JCI119198

Genetic isolation of a region of chromosome 8 that exerts major effects on blood pressure and cardiac mass in the spontaneously hypertensive rat.

V Kren 1, M Pravenec 1, S Lu 1, D Krenova 1, J M Wang 1, N Wang 1, T Merriouns 1, A Wong 1, E St Lezin 1, D Lau 1, C Szpirer 1, J Szpirer 1, T W Kurtz 1
PMCID: PMC507837  PMID: 9045857

Abstract

The spontaneously hypertensive rat (SHR) is the most widely studied animal model of essential hypertension. Despite > 30 yr of research, the primary genetic lesions responsible for hypertension in the SHR remain undefined. In this report, we describe the construction and hemodynamic characterization of a congenic strain of SHR (SHR-Lx) that carries a defined segment of chromosome 8 from a normotensive strain of Brown-Norway rats (BN-Lx strain). Transfer of this segment of chromosome 8 from the BN-Lx strain onto the SHR background resulted in substantial reductions in systolic and diastolic blood pressure and cardiac mass. Linkage and comparative mapping studies indicate that the transferred chromosome segment contains a number of candidate genes for hypertension, including genes encoding a brain dopamine receptor and a renal epithelial potassium channel. These findings demonstrate that BP regulatory gene(s) exist within the differential chromosome segment trapped in the SHR-Lx congenic strain and that this region of chromosome 8 plays a major role in the hypertension of SHR vs. BN-Lx rats.

Full Text

The Full Text of this article is available as a PDF (165.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bazil M. K., Krulan C., Webb R. L. Telemetric monitoring of cardiovascular parameters in conscious spontaneously hypertensive rats. J Cardiovasc Pharmacol. 1993 Dec;22(6):897–905. doi: 10.1097/00005344-199312000-00019. [DOI] [PubMed] [Google Scholar]
  2. Brockway B. P., Mills P. A., Azar S. H. A new method for continuous chronic measurement and recording of blood pressure, heart rate and activity in the rat via radio-telemetry. Clin Exp Hypertens A. 1991;13(5):885–895. doi: 10.3109/10641969109042094. [DOI] [PubMed] [Google Scholar]
  3. Ely D. L., Turner M. E. Hypertension in the spontaneously hypertensive rat is linked to the Y chromosome. Hypertension. 1990 Sep;16(3):277–281. doi: 10.1161/01.hyp.16.3.277. [DOI] [PubMed] [Google Scholar]
  4. Iwai N., Kurtz T. W., Inagami T. Further evidence of the SA gene as a candidate gene contributing to the hypertension in spontaneously hypertensive rat. Biochem Biophys Res Commun. 1992 Oct 15;188(1):64–69. doi: 10.1016/0006-291x(92)92350-7. [DOI] [PubMed] [Google Scholar]
  5. Jacob H. J., Brown D. M., Bunker R. K., Daly M. J., Dzau V. J., Goodman A., Koike G., Kren V., Kurtz T., Lernmark A. A genetic linkage map of the laboratory rat, Rattus norvegicus. Nat Genet. 1995 Jan;9(1):63–69. doi: 10.1038/ng0195-63. [DOI] [PubMed] [Google Scholar]
  6. Katsuya T., Higaki J., Zhao Y., Miki T., Mikami H., Serikawa T., Ogihara T. A neuropeptide Y locus on chromosome 4 cosegregates with blood pressure in the spontaneously hypertensive rat. Biochem Biophys Res Commun. 1993 Apr 15;192(1):261–267. doi: 10.1006/bbrc.1993.1408. [DOI] [PubMed] [Google Scholar]
  7. Kren V. Genetics of the polydactyly-luxate syndrome in the Norway rat, Rattus norvegicus. Acta Univ Carol Med Monogr. 1975;(68):1–103. [PubMed] [Google Scholar]
  8. Kurtz T. W., Simonet L., Kabra P. M., Wolfe S., Chan L., Hjelle B. L. Cosegregation of the renin allele of the spontaneously hypertensive rat with an increase in blood pressure. J Clin Invest. 1990 Apr;85(4):1328–1332. doi: 10.1172/JCI114572. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Lodwick D., Kaiser M. A., Harris J., Cumin F., Vincent M., Samani N. J. Analysis of the role of angiotensinogen in spontaneous hypertension. Hypertension. 1995 Jun;25(6):1245–1251. doi: 10.1161/01.hyp.25.6.1245. [DOI] [PubMed] [Google Scholar]
  10. Nara Y., Nabika T., Ikeda K., Sawamura M., Mano M., Endo J., Yamori Y. Basal high blood pressure cosegregates with the loci on chromosome 1 in the F2 generation from crosses between normotensive Wistar Kyoto rats and stroke-prone spontaneously hypertensive rats. Biochem Biophys Res Commun. 1993 Aug 16;194(3):1344–1351. doi: 10.1006/bbrc.1993.1972. [DOI] [PubMed] [Google Scholar]
  11. OKAMOTO K., AOKI K. Development of a strain of spontaneously hypertensive rats. Jpn Circ J. 1963 Mar;27:282–293. doi: 10.1253/jcj.27.282. [DOI] [PubMed] [Google Scholar]
  12. Pravenec M., Gauguier D., Schott J. J., Buard J., Kren V., Bila V., Szpirer C., Szpirer J., Wang J. M., Huang H. Mapping of quantitative trait loci for blood pressure and cardiac mass in the rat by genome scanning of recombinant inbred strains. J Clin Invest. 1995 Oct;96(4):1973–1978. doi: 10.1172/JCI118244. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Pravenec M., Klír P., Kren V., Zicha J., Kunes J. An analysis of spontaneous hypertension in spontaneously hypertensive rats by means of new recombinant inbred strains. J Hypertens. 1989 Mar;7(3):217–221. [PubMed] [Google Scholar]
  14. Pravenec M., Kren V., Kunes J., Scicli A. G., Carretero O. A., Simonet L., Kurtz T. W. Cosegregation of blood pressure with a kallikrein gene family polymorphism. Hypertension. 1991 Feb;17(2):242–246. doi: 10.1161/01.hyp.17.2.242. [DOI] [PubMed] [Google Scholar]
  15. Pravenec M., Simonet L., Kren V., Kunes J., Levan G., Szpirer J., Szpirer C., Kurtz T. The rat renin gene: assignment to chromosome 13 and linkage to the regulation of blood pressure. Genomics. 1991 Mar;9(3):466–472. doi: 10.1016/0888-7543(91)90412-8. [DOI] [PubMed] [Google Scholar]
  16. Samani N. J., Lodwick D., Vincent M., Dubay C., Kaiser M. A., Kelly M. P., Lo M., Harris J., Sassard J., Lathrop M. A gene differentially expressed in the kidney of the spontaneously hypertensive rat cosegregates with increased blood pressure. J Clin Invest. 1993 Aug;92(2):1099–1103. doi: 10.1172/JCI116616. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Schork N. J., Krieger J. E., Trolliet M. R., Franchini K. G., Koike G., Krieger E. M., Lander E. S., Dzau V. J., Jacob H. J. A biometrical genome search in rats reveals the multigenic basis of blood pressure variation. Genome Res. 1995 Sep;5(2):164–172. doi: 10.1101/gr.5.2.164. [DOI] [PubMed] [Google Scholar]
  18. Simon D. B., Karet F. E., Rodriguez-Soriano J., Hamdan J. H., DiPietro A., Trachtman H., Sanjad S. A., Lifton R. P. Genetic heterogeneity of Bartter's syndrome revealed by mutations in the K+ channel, ROMK. Nat Genet. 1996 Oct;14(2):152–156. doi: 10.1038/ng1096-152. [DOI] [PubMed] [Google Scholar]
  19. St Lezin E. M., Pravenec M., Wong A. L., Liu W., Wang N., Lu S., Jacob H. J., Roman R. J., Stec D. E., Wang J. M. Effects of renin gene transfer on blood pressure and renin gene expression in a congenic strain of Dahl salt-resistant rats. J Clin Invest. 1996 Jan 15;97(2):522–527. doi: 10.1172/JCI118444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. St Lezin E. M., Pravenec M., Wong A., Wang J. M., Merriouns T., Newton S., Stec D. E., Roman R. J., Lau D., Morris R. C., Jr Genetic contamination of Dahl SS/Jr rats. Impact on studies of salt-sensitive hypertension. Hypertension. 1994 Jun;23(6 Pt 1):786–790. doi: 10.1161/01.hyp.23.6.786. [DOI] [PubMed] [Google Scholar]
  21. Turner M. E., Johnson M. L., Ely D. L. Separate sex-influenced and genetic components in spontaneously hypertensive rat hypertension. Hypertension. 1991 Jun;17(6 Pt 2):1097–1103. doi: 10.1161/01.hyp.17.6.1097. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES