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(Hypertension. 2000;35:568.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Contribution of Autosomal Loci and the Y Chromosome to the Stress Response in Rats

Pierre Dumas; Zdenka Pausová; Vladimír Kren; Drahomíra Krenová; Michal Pravenec; Marc Dumont; Daniel Ely; Monte Turner; Yulin Sun; Johanne Tremblay; Pavel Hamet

From the Centre de Recherche du CHUM, Université de Montréal, Montréal, Québec, Canada (P.D., Z.P., M.D., Y.S., J.T., P.H.); the Institute of Biology, First Medical Faculty, Charles University, Prague, Czech Republic (V.K., D.K., M.P.); the Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic (V.K., M.P.); and the Department of Biology, University of Akron, Akron, Ohio (D.E., M.T.).

Correspondence to Johanne Tremblay or Pavel Hamet, Laboratory of Cellular Biology of Hypertension and Laboratory of Molecular Medicine, Centre de Recherche-CHUM, 3850 Rue Saint-Urbain, Montréal, Québec, Canada H2W 1T8. E-mail hamet{at}ere.umontreal.ca

Abstract—Stress is a critical contributor to cardiovascular diseases through its impact on blood pressure variability and cardiac function. Familial clustering of reactivity to stress has been demonstrated in human subjects, and some rodent models of hypertension are hyperresponsive to stress. Therefore, the present study was designed to uncover the genetic determinants of the stress response. We performed a total genome linkage search to identify the loci of the body temperature response to immobilization stress in a set of recombinant inbred strains (RIS) originating from reciprocal crosses of spontaneously hypertensive rats (SHR) with a normotensive Brown Norway Lx strain. Two quantitative trait loci (QTLs) were revealed on chromosomes (Chrs) 10 and 12 (logarithm of odds scores, 2.2 and 1.3, respectively). The effects of these QTLs were enhanced by a high sodium diet (logarithm of odds scores, 4.0 and 3.3 for Chrs 10 and 12, respectively), which is suggestive of a salt-sensitive component for the phenotype. Congenics for Chr 10 confirmed both the QTL and the salt effect in RIS. Negatively associated loci were also identified on Chrs 8 and 11. Interaction between the loci of Chrs 10 and 12 was demonstrated, with the rat strains bearing SHR alleles at both loci having the highest thermal response to stress. Furthermore, the Y Chr of SHR origin enhanced the response to immobilization stress, as demonstrated in 2 independent models, RIS and Y Chr consomics. However, its full effect requires autosomes of the SHR strain. These findings provide the first evidence for the genetic determination of reactivity to stress with interactions between autosomal loci and between the Y and autosomal Chrs that contribute to the explanation of the 46% of variance in the stress response.

Key Words: stress • linkage (genetic) • quantitative trait • sex chromosomes

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