title: Endothelial dysfunction and blood pressure variability in selected inbred mouse strains.
abstract: The genetic regulation of blood pressure (BP) and endothelial function is likely to be polygenic. Because there is considerable variability in basal BP among inbred mouse strains, the purpose of this study was to determine whether a similar variability in vascular function exists among 7 "normotensive" strains. We tested the hypothesis that compared with mice with higher BPs, mice with lower BPs would have greater aortic endothelial responses to acetylcholine (ACh). Mean BP ranged from 117 to 145 mm Hg among the 7 strains. The responses of aortic rings to ACh, sodium nitroprusside, and papaverine were assessed after submaximal precontraction with prostaglandin F(2alpha). The aortas from all strains relaxed in a concentration-dependent manner to sodium nitroprusside and papaverine, but responses to ACh were markedly impaired in the aortas, but not carotid arteries, from 129P3/J and 129X1/SvJ mice. Aortas from the other strains relaxed normally to ACh. Furthermore, the endothelium-dependent dilators ADP and A23187 caused similar relaxation in 129P3/J, 129X1/SvJ, and C57BL/6J mice. Although the data do not support the initial hypothesis, the impaired aortic response to ACh in the 129 strains is a novel finding and illustrates the potential impact that genetic background can have on vascular responsiveness.
authors.affiliation: Department of Internal Medicine, Cardiovascular Center, University of Iowa, Iowa City 52242, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ryan
authors.forename: Sean P
authors.initials: SP
authors.lastname: Didion
authors.forename: Deborah R
authors.initials: DR
authors.lastname: Davis
authors.forename: Frank M
authors.initials: FM
authors.lastname: Faraci
authors.forename: Curt D
authors.initials: CD
authors.lastname: Sigmund
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D001795:Blood Pressure Determination; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000502:physiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics / Q000502:physiology*; D023421:Models, Animal; D013045:Species Specificity; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D000109:Acetylcholine