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Am J Physiol Regul Integr Comp Physiol (May 28, 2008). doi:10.1152/ajpregu.00038.2008
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Submitted on January 20, 2008
Accepted on May 21, 2008

Sex-Specific Differences in Chromosome-Dependent Regulation of Vascular Reactivity in Female Consomic Rat Strains from a SS x BN Cross

Mary Pat Kunert1*, Melinda R Dwinell2, Ines Drenjancevic-Peric2, and Julian H. Lombard3

1 Nursing, UW-Milwaukee, Milwaukee, Wisconsin, United States
2 Physiology, Medical College of Wisconsin, 53226, Wisconsin, United States
3 Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States

* To whom correspondence should be addressed. E-mail: mpkunert{at}uwm.edu.

High-throughput studies in the Medical College of Wisconsin Program for Genomic Applications (Physgen) were designed to link chromosomes with physiological function in consomic strains derived from a cross between Dahl salt sensitive SS/JrHsdMcwi (SS) and Brown Norway normotensive BN/NHsdMcwi (BN) rats. The specific goal of the vascular protocol was to characterize the responses of aortic rings from these strains to vasoconstrictor and vasodilator stimuli (phenylephrine, acetylcholine, sodium nitroprusside and bath hypoxia) in order to identify chromosomes that either increase or decrease vascular reactivity to these vasoactive stimuli. Because previous studies demonstrated sex-specific quantitative trait loci (QTLs) related to regulation of cardiovascular phenotypes in an F2 cross between the parental strains, males and females of each consomic strain were included in all experiments. As there were significant sex-specific differences in aortic sensitivity to vasoconstrictor and vasodilator stimuli compared to the parental SS strain, we report the results of the females separately from the males. There were also sex-specific differences in aortic ring sensitivity to these vasoactive stimuli in consomic strains that were fed a high salt diet (4% NaCl) for three weeks to evaluate salt-induced changes in vascular reactivity. Differences in genetic architecture could contribute to sex-specific differences in the development and expression of cardiovascular diseases via differential regulation and expression of genes. Our findings are the first to link physiological traits with specific chromosomes in female SS rats, and support the idea that sex is an important environmental variable that plays a role in the expression and regulation of genes.







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