title: Distinct genomic replacements from Lewis correct diastolic dysfunction, attenuate hypertension, and reduce left ventricular hypertrophy in Dahl salt-sensitive rats.
abstract: BACKGROUND
  Hypertension and diastolic heart failure are two common cardiovascular diseases that inflict heavy morbidity and mortality, yet relatively little is understood about their pathophysiology. The identification of quantitative trait loci for blood pressure is important in unveiling the causes of polygenic hypertension. Although Dahl salt-sensitive strain is also an excellent model for the study of diastolic heart failure, virtually nothing is known about the quantitative trait loci determining diastolic heart failure. Diastolic dysfunction often represents the onset of diastolic heart failure.
  
  
  METHODS
  We first characterized the cardiac phenotype of Dahl salt-sensitive strain and normotensive Lewis control rats by echocardiography to ascertain diastolic function. We then analyzed corresponding features of four newly developed and two existing congenic strains, each of which carries a specific chromosome substitution of Dahl salt-sensitive strain by its Lewis homologue and each lowering blood pressure.
  
  
  RESULTS
  Dahl salt-sensitive strain displayed diastolic dysfunction that was rectified in two of six congenic strains, designated as positive congenic strains, which represent the first rodent models exhibiting functional normalization of diastolic dysfunction caused by naturally occurring genetic variants. The two positive congenic strains also showed a reduction in left ventricular mass. In contrast, four of six congenic strains did not change diastolic function despite their blood pressure-lowering effects.
  
  
  CONCLUSIONS
  Genes present in the replaced chromosome segments of the two positive congenic strains are not commonly known to affect blood pressure, diastolic function or left ventricular mass. Consequently, novel prognostic, diagnostic and therapeutic strategies for hypertensive diastolic heart failure likely emerge from this work.
authors.affiliation: Research Centre, Centre hospitalier de l'Université de Montréal, Montréal, Québec, Canada. alan.deng@umontreal.ca
authors.forename: Alan Y
authors.initials: AY
authors.lastname: Deng
authors.forename: Stanley
authors.initials: S
authors.lastname: Nattel
authors.forename: Yanfen
authors.initials: Y
authors.lastname: Shi
authors.forename: Nathalie
authors.initials: N
authors.lastname: L'heureux
authors.forename: Sophie
authors.initials: S
authors.lastname: Cardin
authors.forename: Annie
authors.initials: A
authors.lastname: Ménard
authors.forename: Julie
authors.initials: J
authors.lastname: Roy
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Tardif
mesh_terms: D000818:Animals; D006973:Hypertension / Q000235:genetics*; D008297:Male; D040641:Quantitative Trait Loci; D051381:Rats; D020303:Rats, Inbred Dahl / Q000235:genetics; D011917:Rats, Inbred Lew / Q000235:genetics; D014463:Ultrasonography; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000235:genetics*