title: Identification of a region of rat chromosome 1 that impairs the myogenic response and autoregulation of cerebral blood flow in fawn-hooded hypertensive rats.
abstract: This study examined the effects of transfer of a 2.4-Mbp region of rat chromosome 1 (RNO1) from Brown Norway (BN) into fawn-hooded hypertensive (FHH) rats on autoregulation (AR) of cerebral blood flow (CBF) and the myogenic response of middle cerebral arteries (MCAs). AR of CBF was poor in FHH and FHH.1(BN) AR(-) congenic strains that excluded the critical 2.4-Mbp region. In contrast, AR was restored in FHH.1(BN) AR(+) congenic strains that included this region. The diameter of MCAs of FHH rats increased from 140 ± 14 to 157 ± 18 μm when transmural pressure was increased from 40 to 140 mmHg, but it decreased from 137 ± 5 to 94 ± 7 μm in FHH.1(BN) AR(+) congenic strains. Transient occlusion of MCAs reduced CBF by 80% in all strains. However, the hyperemic response following ischemia was significantly greater in FHH and AR(-) rats than that seen in AR(+) congenic strains (AR(-), 173 ± 11% vs. AR(+), 124 ± 5%). Infarct size and edema formation were also significantly greater in an AR(-) strain (38.6 ± 2.6 and 12.1 ± 2%) than in AR(+) congenic strains (27.6 ± 1.8 and 6.5 ± 0.9%). These results indicate that there is a gene in the 2.4-Mbp region of RNO1 that alters the development of myogenic tone in cerebral arteries. Transfer of this region from BN to FHH rats restores AR of CBF and vascular reactivity and reduces cerebral injury after transient occlusion and reperfusion of the MCA.
authors.affiliation: Human and Molecular Genetics Center, Milwaukee, WI, USA.
authors.forename: Mallikarjuna R
authors.initials: MR
authors.lastname: Pabbidi
authors.forename: Julio
authors.initials: J
authors.lastname: Juncos
authors.forename: Luis
authors.initials: L
authors.lastname: Juncos
authors.forename: Marija
authors.initials: M
authors.lastname: Renic
authors.forename: Hurtis J
authors.initials: HJ
authors.lastname: Tullos
authors.forename: Jozeph
authors.initials: J
authors.lastname: Lazar
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Jacob
authors.forename: David R
authors.initials: DR
authors.lastname: Harder
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Roman
mesh_terms: D000818:Animals; D020296:Animals, Congenic; D001794:Blood Pressure / Q000235:genetics*; D001929:Brain Edema / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control; D002560:Cerebrovascular Circulation / Q000235:genetics*; D033481:Chromosomes, Mammalian; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D020022:Genetic Predisposition to Disease; D006706:Homeostasis; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D020768:Middle Cerebral Artery / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D010641:Phenotype; D051381:Rats; D011914:Rats, Inbred BN; D015427:Reperfusion Injury / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control