title: Genetic basis of the impaired renal myogenic response in FHH rats.
abstract: This study examined the effect of substitution of a 2.4-megabase pair (Mbp) region of Brown Norway (BN) rat chromosome 1 (RNO1) between 258.8 and 261.2 Mbp onto the genetic background of fawn-hooded hypertensive (FHH) rats on autoregulation of renal blood flow (RBF), myogenic response of renal afferent arterioles (AF-art), K(+) channel activity in renal vascular smooth muscle cells (VSMCs), and development of proteinuria and renal injury. FHH rats exhibited poor autoregulation of RBF, while FHH.1BN congenic strains with the 2.4-Mbp BN region exhibited nearly perfect autoregulation of RBF. The diameter of AF-art from FHH rats increased in response to pressure but decreased in congenic strains containing the 2.4-Mbp BN region. Protein excretion and glomerular and interstitial damage were significantly higher in FHH rats than in congenic strains containing the 2.4-Mbp BN region. K(+) channel current was fivefold greater in VSMCs from renal arterioles of FHH rats than cells obtained from congenic strains containing the 2.4-Mbp region. Sequence analysis of the known and predicted genes in the 2.4-Mbp region of FHH rats revealed amino acid-altering variants in the exons of three genes: Add3, Rbm20, and Soc-2. Quantitative PCR studies indicated that Mxi1 and Rbm20 were differentially expressed in the renal vasculature of FHH and FHH.1BN congenic strain F. These data indicate that transfer of this 2.4-Mbp region from BN to FHH rats restores the myogenic response of AF-art and autoregulation of RBF, decreases K(+) current, and slows the progression of proteinuria and renal injury.
authors.affiliation: Dept. of Pharmacology and Toxicology, Univ. of Mississippi Medical Center, 2500 North State St. Jackson, MS 39216, USA.
authors.forename: Marilyn
authors.initials: M
authors.lastname: Burke
authors.forename: Malikarjuna
authors.initials: M
authors.lastname: Pabbidi
authors.forename: Fan
authors.initials: F
authors.lastname: Fan
authors.forename: Ying
authors.initials: Y
authors.lastname: Ge
authors.forename: Ruisheng
authors.initials: R
authors.lastname: Liu
authors.forename: Jan Michael
authors.initials: JM
authors.lastname: Williams
authors.forename: Allison
authors.initials: A
authors.lastname: Sarkis
authors.forename: Jozef
authors.initials: J
authors.lastname: Lazar
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Jacob
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Roman
mesh_terms: D000818:Animals; D001160:Arterioles / Q000503:physiopathology*; D001794:Blood Pressure / Q000502:physiology; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000503:physiopathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D011507:Proteinuria / Q000235:genetics / Q000503:physiopathology; D051381:Rats; D011914:Rats, Inbred BN; D012079:Renal Circulation / Q000502:physiology*; D051437:Renal Insufficiency / Q000235:genetics / Q000503:physiopathology