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Am J Physiol Regul Integr Comp Physiol 295: R516-R527, 2008. First published May 28, 2008; doi:10.1152/ajpregu.00038.2008
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HEMODYNAMICS AND CARDIORENAL INTEGRATION

Sex-specific differences in chromosome-dependent regulation of vascular reactivity in female consomic rat strains from a SS x BN cross

Mary Pat Kunert,1,2 Melinda R. Dwinell,2 Ines Drenjancevic Peric,2 and Julian H. Lombard2

1College of Nursing, University of Wisconsin-Milwaukee; and 2Medical College of Wisconsin, Milwaukee, Wisconsin

Submitted 20 January 2008 ; accepted in final form 21 May 2008

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) 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 with 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 3 wk 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.

phenylephrine; acetylcholine; sodium nitroprusside; hypoxia; aortic rings


Address for reprint requests and other correspondence: M. P. Kunert, College of Nursing, Univ. of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53211 (e-mail: mpkunert{at}uwm.edu)






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