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(Hypertension. 2001;37:1147.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Y-Chromosome Transfer Induces Changes in Blood Pressure and Blood Lipids in SHR

Vladimir Kren¹; Nianning Qi¹; Drahomira Krenova; Vaclav Zidek; Milada Sladká; Marie Jáchymová; Blanka Míková; Karel Horky; Anita Bonne; Hein A. Van Lith; Bert F. M. Van Zutphen; Yun-Fai Chris Lau; Michal Pravenec; Elizabeth St. Lezin

From the Institute of Biology and Medical Genetics (V.K., D.K., M.S., M.P.), General Faculty Hospital (M.J., B.M., K.H.), First Medical Faculty, Charles University, Prague, Czech Republic; the Institute of Physiology (V.K., V.Z., M.P.), Czech Academy of Science, Prague, Czech Republic; the Department of Laboratory Medicine (N.Q., E.S.) and the Department of Medicine (Y.-F.C.L.), University of California, San Francisco; and the Department of Laboratory Animal Science (A.B., H.A.V.L., B.F.M.V.Z.), Veterinary Faculty, Utrecht University, Utrecht, The Netherlands.

Correspondence to Elizabeth St. Lezin, MD, Department of Laboratory Medicine, San Francisco VA Medical Center 113A, 4150 Clement St, San Francisco, CA 94121. E-mail stlezine{at}labmed2.ucsf.edu

Abstract—Previous studies with chromosome-Y consomic strains of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats suggest that a quantitative trait locus for blood pressure regulation exists on chromosome Y. To test this hypothesis in the SHR–Brown Norway (BN) model and to study the effects of chromosome Y on lipid and carbohydrate metabolism, we produced a new consomic strain of SHR carrying the Y chromosome transferred from the BN rat. We found that replacing the SHR Y chromosome with the BN Y chromosome resulted in significant decreases in systolic and diastolic blood pressures in the SHR.BN-Y consomic strain (P<0.05). To elicit possible dietary-induced variation in lipid and glucose metabolism between the SHR progenitor and chromosome-Y consomic strains, we fed rats a high-fructose diet for 15 days in addition to the normal diet. On the high-fructose diet, the SHR.BN-Y consomic rats exhibited significantly increased levels of serum triglycerides and decreased levels of serum HDL cholesterol versus the SHR progenitor rats. Glucose tolerance and insulin/glucose ratios, however, were similar in both strains on both normal and high-fructose diets. These findings provide direct evidence that a gene or genes on chromosome Y contribute to the pathogenesis of spontaneous hypertension in the SHR-BN model. These results also indicate that transfer of the Y chromosome from the BN rat onto the SHR background exacerbates dietary-induced dyslipidemia in SHR. Thus, genetic variation in genes on the Y chromosome may contribute to variation in blood pressure and lipid levels and may influence the risk for cardiovascular disease.

Key Words: hypertension, genetic • rats, spontaneously hypertensive • cholesterol • genes • lipids • cardiovascular disease

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