RGD Reference Report - Combining distinctive and novel loci doubles BP reduction, reverses diastolic dysfunction and mitigates LV hypertrophy. - Rat Genome Database

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Combining distinctive and novel loci doubles BP reduction, reverses diastolic dysfunction and mitigates LV hypertrophy.

Authors: Crespo, K  Chauvet, C  Menard, A  Roy, J  Shi, Y  Gelinas, D  Duval, F  L'heureux, N  Nattel, S  Tardif, JC  Deng, AY 
Citation: Crespo K, etal., J Hypertens. 2013 May;31(5):927-35. doi: 10.1097/HJH.0b013e32835edc7e.
RGD ID: 8657131
Pubmed: PMID:23442991   (View Abstract at PubMed)
DOI: DOI:10.1097/HJH.0b013e32835edc7e   (Journal Full-text)

OBJECTIVES: 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. CONCLUSION: 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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
LEW/CrlcRatDiastolic Dysfunction MODEL: controlIAGPcontrolled sodium content dietcompared to SS/JrHsd and congenic strainsRGD 
SS/JrHsdRatDiastolic Dysfunction MODEL: inducedIAGPcontrolled sodium content dietcompared to Lewis and congenic strainsRGD 
SS/JrHsdRathypertension MODEL: inducedIAGPcontrolled sodium content dietcompared to Lewis and congenic strainsRGD 
LEW/CrlcRatLeft Ventricular Hypertrophy MODEL: controlIAGPcontrolled sodium content dietcompared to SS/JrHsd and congenic strainsRGD 
SS/JrHsdRatLeft Ventricular Hypertrophy MODEL: inducedIAGPcontrolled sodium content dietcompared to Lewis and congenic strainsRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SS.LEW-(D17Chm131-D17Chm93),MNS-(D2Rat155-D2Chm161),LEW-(D18Chm41-D18Rat92)/AydRatdecreased left ventricle developed pressure  IAGP  RGD 
SS.MNS-(D2Chm254-D2Chm161),LEW-(D10Chm246-D10Chm257),LEW-(D16Chm48-D16Chm60),LEW-(D18Rat55-D18Mgh2)/AydRatdecreased left ventricle developed pressure  IAGP  RGD 
SS.MNS-(D2Chm366-D2Rat52),LEW-(D18Rat61-D18Rat45),LEW-(D10Chm128-D10Chm121)/AydRatdecreased left ventricle developed pressure  IAGP  RGD 
LEW/CrlcRatdecreased systemic arterial systolic blood pressure  IAGP compared to SS/JrHsdRGD 
SS.LEW-(D18Chm41-D18Rat92)/AydRatdecreased systemic arterial systolic blood pressure  IAGP compared to SS/JrHsdRGD 
SS.LEW-(D18Rat61-D18Rat45)/AydRatdecreased systemic arterial systolic blood pressure  IAGP compared to SS/JrHsdRGD 
SS.LEW-(D10Chm280-D10Chm216)/AydRatdecreased systemic arterial systolic blood pressure  IAGP compared to SS/JrHsdRGD 
SS.LEW-(D16Chm48-D16Chm60)/AydRatdecreased systemic arterial systolic blood pressure  IAGP compared to SS/JrHsdRGD 
SS.LEW-(D17Chm131-D17Chm93),MNS-(D2Rat155-D2Chm161),LEW-(D18Chm41-D18Rat92)/AydRatdecreased systemic arterial systolic blood pressure  IAGP  RGD 
SS.LEW-(D17Chm131-D17Chm93)/AydRatdecreased systemic arterial systolic blood pressure  IAGP compared to SS/JrHsdRGD 
SS.LEW-(D18Rat55-D18Mgh2)/AydRatdecreased systemic arterial systolic blood pressure  IAGP compared to SS/JrHsdRGD 
SS.MNS-(D2Chm254-D2Chm161),LEW-(D10Chm246-D10Chm257),LEW-(D16Chm48-D16Chm60),LEW-(D18Rat55-D18Mgh2)/AydRatdecreased systemic arterial systolic blood pressure  IAGP compared to SS/JrHsdRGD 
SS.MNS-(D2Chm254-D2Chm161)/AydRatdecreased systemic arterial systolic blood pressure  IAGP compared to SS/JrHsdRGD 
SS.MNS-(D2Chm366-D2Rat52),LEW-(D18Rat61-D18Rat45),LEW-(D10Chm128-D10Chm121)/AydRatdecreased systemic arterial systolic blood pressure  IAGP compared to SS/JrHsdRGD 
SS.MNS-(D2Chm366-D2Rat52)/AydRatdecreased systemic arterial systolic blood pressure  IAGP compared to SS/JrHsdRGD 
SS.MNS-(D2Rat155-D2Chm161)/AydRatdecreased systemic arterial systolic blood pressure  IAGP compared to SS/JrHsdRGD 
SS.LEW-(D10Chm280-D10Chm216)/AydRatheart left ventricle hypertrophy  IAGPcontrolled sodium content dietcompared to LewisRGD 
SS.LEW-(D16Chm48-D16Chm60)/AydRatheart left ventricle hypertrophy  IAGPcontrolled sodium content dietcompared to LewisRGD 
SS.LEW-(D17Chm131-D17Chm93),MNS-(D2Rat155-D2Chm161),LEW-(D18Chm41-D18Rat92)/AydRatheart left ventricle hypertrophy  IAGPcontrolled sodium content dietcompared to LewisRGD 
SS.LEW-(D17Chm131-D17Chm93)/AydRatheart left ventricle hypertrophy  IAGPcontrolled sodium content dietcompared to LewisRGD 
SS.MNS-(D2Chm254-D2Chm161),LEW-(D10Chm246-D10Chm257),LEW-(D16Chm48-D16Chm60),LEW-(D18Rat55-D18Mgh2)/AydRatheart left ventricle hypertrophy  IAGPcontrolled sodium content dietcompared to LewisRGD 
SS.MNS-(D2Chm366-D2Rat52),LEW-(D18Rat61-D18Rat45),LEW-(D10Chm128-D10Chm121)/AydRatheart left ventricle hypertrophy  IAGPcontrolled sodium content dietcompared to LewisRGD 
SS/JrHsdRatheart left ventricle hypertrophy  IAGPcontrolled sodium content dietcompared to LewisRGD 
SS/JrHsdRatincreased cardiac muscle contractility susceptibilityIAGP compared to Lewis ratRGD 

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Objects referenced in this article
Strain LEW/NHsd null Rattus norvegicus

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