Sex-specific differences in chromosome-dependent regulation of vascular reactivity in female consomic rat strains from a SSxBN cross.
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.
Kunert
Mary Pat
MP
College of Nursing, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53211, USA. mpkunert@uwm.edu
Dwinell
Melinda R
MR
Drenjancevic Peric
Ines
I
Lombard
Julian H
JH
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects; D015687:Cell Hypoxia; D033481:Chromosomes, Mammalian; D003433:Crosses, Genetic; D005260:Female; D005838:Genotype; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010641:Phenotype; D010656:Phenylephrine / Q000494:pharmacology; D040641:Quantitative Trait Loci; D051381:Rats; D011914:Rats, Inbred BN; D020303:Rats, Inbred Dahl; D012737:Sex Factors; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage; D014661:Vasoconstriction / Q000187:drug effects / Q000235:genetics*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000235:genetics*; D014665:Vasodilator Agents / Q000494:pharmacology
D017673:Sodium Chloride, Dietary; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D000109:Acetylcholine