Identification of a region of rat chromosome 1 that impairs the myogenic response and autoregulation of cerebral blood flow in fawn-hooded hypertensive rats. Am J Physiol Heart Circ Physiol 2013 Jan 15;304(2):H311-7
Date
11/13/2012Pubmed ID
23144316Pubmed Central ID
PMC3543673DOI
10.1152/ajpheart.00622.2012Scopus ID
2-s2.0-84872388133 (requires institutional sign-in at Scopus site) 19 CitationsAbstract
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.
Author List
Pabbidi MR, Juncos J, Juncos L, Renic M, Tullos HJ, Lazar J, Jacob HJ, Harder DR, Roman RJMESH terms used to index this publication - Major topics in bold
AnimalsAnimals, Congenic
Blood Pressure
Brain Edema
Cerebrovascular Circulation
Chromosomes, Mammalian
Disease Models, Animal
Gene Transfer Techniques
Genetic Predisposition to Disease
Homeostasis
Hypertension
Infarction, Middle Cerebral Artery
Male
Middle Cerebral Artery
Muscle, Smooth, Vascular
Phenotype
Rats
Rats, Inbred BN
Reperfusion Injury
