title: Interaction between chromosome 2 and 3 regulates pulse pressure in the stroke-prone spontaneously hypertensive rat.
abstract: In an F2 cross between stroke-prone spontaneously hypertensive (SHRSP) and Wistar Kyoto (WKY) rats, we previously identified blood pressure quantitative trait loci (QTL) on rat chromosome (RNO) 2 and a pulse pressure QTL on RNO3. The aims of this study were to confirm the QTL on RNO3 and to investigate interaction between RNO2 and RNO3 loci through the generation and phenotypic assessment of single RNO3 congenic (SP.WKY(Gla)3a) and bicongenic (SP.WKY(Gla)2a/3a) strains. Hemodynamic profiling, vascular function, and renal histology were examined in these newly generated strains along with the previously reported RNO2 congenic strain (SP.WKY(Gla)2a). Our results demonstrate significant equivalent reduction in systolic, diastolic, and pulse pressure phenotypes in SP.WKY(Gla)3a and SP.WKY(Gla)2a rats, whereas greater reductions were observed with the SP.WKY(Gla)2a/3a bicongenic strain achieving blood pressure levels similar to normotensive WKY rats. Epistasis was observed between pulse pressure QTL on RNO2 and 3 at baseline and during 1% salt challenge. Vascular function and renal pathology studies indicate that QTL on RNO3 are responsible for salt-induced kidney pathology, whereas QTL on RNO2 seem to have greater impact on vascular function. RNO3 congenic and bicongenic strains have confirmed the importance of SHRSP alleles in the RNO3 congenic interval on pulse pressure variability and end-organ damage. These strains will allow interrogation of complex gene-gene and gene-environment interactions contributing to salt-sensitive hypertension and renal pathology in the SHRSP rat.
authors: Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
authors: H H Caline
authors: HH
authors: Koh-Tan
authors: Martin W
authors: MW
authors: McBride
authors: John D
authors: JD
authors: McClure
authors: Elisabeth
authors: E
authors: Beattie
authors: Barbara
authors: B
authors: Young
authors: Anna F
authors: AF
authors: Dominiczak
authors: Delyth
authors: D
authors: Graham
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000503:physiopathology; D001794:Blood Pressure / Q000502:physiology*; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics*; D004195:Disease Models, Animal; D059647:Gene-Environment Interaction; D006973:Hypertension / Q000150:complications / Q000235:genetics* / Q000473:pathology; D007668:Kidney / Q000473:pathology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020521:Stroke / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D014661:Vasoconstriction / Q000235:genetics; D016277:Ventricular Function, Left
keywords: Wistar Kyoto; bicongenic strains; congenic strains; epistasis; pulse pressure; renal pathology; stroke-prone spontaneously hypertensive