Abstract

Our recent studies have shown that a primary genetic component of hypertension in the spontaneously hypertensive rat (SHR) is on the Y chromosome. We have developed two new, unique F12 substrains of SHR designated SHR/y and SHR/a, which allow the manipulation of the effects of the Y chromosome. The SHR/y substrain contains a hypertensive Y chromosome in a normotensive autosomal background. The SHR/a substrain contains a normotensive Y chromosome in a hypertensive autosomal background. The hypothesis of this study is that the sympathetic nervous system and the testes interact to produce an elevated blood pressure that is sex linked and one component is ont he Y chromosome. To accomplish this we will: 1) determine the impact of the Y chromosome on sympathetic nervous system responsiveness and the testes, and 2) determine the genetic interaction of the Y chromosome in hypertensive and normotensive genetic backgrounds. Preliminary data suggests that the sympathetic nervous system (SNS) is modulated by the hypertensive Y chromosome. By comparing central and peripheral SNS indicators, steroid profiles, salt sensitivity and salt appetite in the SHR/y and SHR/a substrains we will determine which of these parameters are influenced by the Y chromosome. Based on our results of backcross progeny, the dominant/recessive relationship of the SHR and WKY hypertensive autosomal genes is modified by the Y chromosome. Crosses between the SHR/y and SHR/a substrains and SHR and WKY will be used to investigate this interaction. Finally, matings of our SHR/y substrain to other normotensive inbred rat strains will be used to determine the effect of the hypertensive Y chromosome in other genetic backgrounds to discover modifier loci.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL048072-03
Application #
2224127
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1993-05-01
Project End
1996-04-30
Budget Start
1995-05-01
Budget End
1996-04-30
Support Year
3
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
University of Akron
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
City
Akron
State
OH
Country
United States
Zip Code
44325

  Publications

Toot, Jonathan; Dunphy, Gail; Turner, Monte et al. (2004) The SHR Y-chromosome increases testosterone and aggression, but decreases serotonin as compared to the WKY Y-chromosome in the rat model. Behav Genet 34:515-24
Caplea, Ann; Seachrist, Darcie; Daneshvar, Hamid et al. (2002) Noradrenergic content and turnover rate in kidney and heart shows gender and strain differences. J Appl Physiol 92:567-71
Caplea, A; Seachrist, D; Dunphy, G et al. (2001) Sodium-induced rise in blood pressure is suppressed by androgen receptor blockade. Am J Physiol Heart Circ Physiol 280:H1793-801
Ely, D; Turner, M; Milsted, A (2000) Review of the Y chromosome and hypertension. Braz J Med Biol Res 33:679-91
Neves, L A; Santos, R A; Khosla, M C et al. (2000) Angiotensin-(1-7) regulates the levels of angiotensin II receptor subtype AT1 mRNA differentially in a strain-specific fashion. Regul Pept 95:99-107
Valigora, S D; Lib, P K; Dunphy, G et al. (2000) Steroid sulfatase inhibitor alters blood pressure and steroid profiles in hypertensive rats. J Steroid Biochem Mol Biol 73:113-22
Seachrist, D; Dunphy, G; Daneshvar, H et al. (2000) Testosterone increases blood pressure and cardiovascular and renal pathology in spontaneously hypertensive rats. Blood Press 9:227-38
Caplea, A; Seachrist, D; Dunphy, G et al. (2000) SHR Y chromosome enhances the nocturnal blood pressure in socially interacting rats. Am J Physiol Heart Circ Physiol 279:H58-66
Dumas, P; Pausova, Z; Kren, V et al. (2000) Contribution of autosomal loci and the Y chromosome to the stress response in rats. Hypertension 35:568-73
Ely, D; Herman, M; Ely, L et al. (2000) Sodium intake is increased by social stress and the Y chromosome and reduced by clonidine. Am J Physiol Regul Integr Comp Physiol 278:R407-12

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