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Sex-specific differences in chromosome-dependent regulation of vascular reactivity in female consomic rat strains from a SSxBN cross. Am J Physiol Regul Integr Comp Physiol 2008 Aug;295(2):R516-27 PMID: 18509103 PMCID: PMC2519925

Pubmed ID

18509103

DOI

10.1152/ajpregu.00038.2008

Abstract

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.

Author List

Kunert MP, Dwinell MR, Drenjancevic Peric I, Lombard JH

Authors

Melinda R. Dwinell PhD Center Associate Director, Associate Professor in the Physiology department at Medical College of Wisconsin
Julian H. Lombard PhD Professor in the Physiology department at Medical College of Wisconsin




Scopus

2-s2.0-51149109894   7 Citations

MESH terms used to index this publication - Major topics in bold

Acetylcholine
Animals
Aorta
Cell Hypoxia
Chromosomes, Mammalian
Crosses, Genetic
Female
Genotype
Male
Nitroprusside
Phenotype
Phenylephrine
Quantitative Trait Loci
Rats
Rats, Inbred BN
Rats, Inbred Dahl
Sex Factors
Sodium Chloride, Dietary
Vasoconstriction
Vasoconstrictor Agents
Vasodilation
Vasodilator Agents
jenkins-FCD Prod-332 f92a19b0ec5e8e1eff783fac390ec127e367c2b5