title: Combining distinctive and novel loci doubles BP reduction, reverses diastolic dysfunction and mitigates LV hypertrophy.
abstract: OBJECTIVE
  Diastolic dysfunction often represents the onset of diastolic heart failure (DHF). We previously showed in principle that diastolic function in Dahl salt-sensitive rats (DSS) can be genetically determined by quantitative trait loci (QTLs) that also modulate blood pressure (BP).
  
  
  METHODS
  We analyzed cardiac phenotypes of four 'single' congenic strains by echocardiography, in which a specific DSS chromosome segment was replaced by its normotensive Lewis homologue.
  
  
  RESULTS
  Two of the strains permanently lowered BP, and but attenuated diastolic dysfunction only in rats at 10 weeks of age, not at 15 weeks fed on a 2% NaCl diet starting from 8 weeks of age. We then combined multiple QTLs by integrating several 'single' congenic strains. As a result, BP was greatly reduced. Cardiac dysfunction and LV hypertrophy were continuously improved from 10 to 15 weeks, although the degree and timing of the improvement varied among different congenic combinations.
  
  
  CONCLUSIONS
  Distinct QTLs exist that simultaneously modulate BP and diastolic function. These QTLs, in combination, synergistically lowered BP and permanently alleviated or reversed diastolic dysfunction. The genes that are contained in the congenic strains affecting diastolic function are not known for their specific influence on BP. Novel long-term strategies of prognosis, diagnosis and therapy for hypertensive DHF appear from this work.
authors: Research Centre, Centre hospitalier de l'Université de Montréal, Québec, Canada.
authors: Kimberley
authors: K
authors: Crespo
authors: Cristina
authors: C
authors: Chauvet
authors: Annie
authors: A
authors: Ménard
authors: Julie
authors: J
authors: Roy
authors: Yanfen
authors: Y
authors: Shi
authors: Danielle
authors: D
authors: Gelinas
authors: Francine
authors: F
authors: Duval
authors: Nathalie
authors: N
authors: L'heureux
authors: Stanley
authors: S
authors: Nattel
authors: Jean-Claude
authors: JC
authors: Tardif
authors: Alan Y
authors: AY
authors: Deng
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000235:genetics*; D003971:Diastole / Q000235:genetics* / Q000502:physiology; D004398:Dyneins / Q000235:genetics; D006973:Hypertension / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000235:genetics*; D008297:Male; D040641:Quantitative Trait Loci; D051381:Rats; D020303:Rats, Inbred Dahl
chemical_list: D004398:Dyneins