RGD Reference Report - Genetic analysis of salt-sensitive hypertension in Dahl rats reveals a link between cardiac fibrosis and high cholesterol. - Rat Genome Database

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Genetic analysis of salt-sensitive hypertension in Dahl rats reveals a link between cardiac fibrosis and high cholesterol.

Authors: Wendt, N  Schulz, A  Qadri, F  Bolbrinker, J  Kossmehl, P  Winkler, K  Stoll, M  Vetter, R  Kreutz, R 
Citation: Wendt N, etal., Cardiovasc Res. 2009 Feb 15;81(3):618-26. Epub 2008 Sep 29.
RGD ID: 2307185
Pubmed: PMID:18824493   (View Abstract at PubMed)
DOI: DOI:10.1093/cvr/cvn263   (Journal Full-text)

AIMS: Previously we confirmed an important role of rat chromosome 19 (RNO19) for salt-sensitive hypertension and target organ damage in male Dahl salt-sensitive rats (SS rats). The aim of this study was to further analyse the basis of left ventricular (LV) fibrosis development in both male and female rats in this model. To this end we utilized a consomic SS-19(SHR) rat strain in which RNO19 was transferred from spontaneously hypertensive rats (SHR) into the susceptible background of SS. METHODS AND RESULTS: We compared the effects of low- (0.2% NaCl) and high-salt (4% NaCl) diet on the development of hypertension, blood lipids and LV fibrosis in male and female SS, SHR, and SS-19(SHR) rats. Systolic blood pressure was significantly lower in male and female SS-19(SHR) compared with SS under both diets (P < 0.001). Relative LV weight was similarly reduced in SS-19(SHR) compared with SS in either sex. Plasma cholesterol concentrations were significantly elevated in high-salt fed male and female SS (141 +/- 6 and 110 +/- 7 mg/dL) compared with SHR (47 +/- 2 and 62 +/- 8 mg/dL, P < 0.001) and were significantly lowered in male and female consomic rats (100 +/- 7 and 87 +/- 3 mg/dL). Both LV interstitial fibrosis (LVIF) and perivascular fibrosis (LVPF) were significantly reduced in high-salt male and female SS-19(SHR). A significant correlation between cholesterol concentrations and LVPF (r = 0.464) and LVIF (r = 0.401, P < 0.0001, respectively) was detected. Fibrosis parameters demonstrated no correlation with blood pressure, LV weight or plasma triglycerides concentrations. LV immunohistochemistry analysis showed a significant higher number of ED-1 positive cells in SS compared with SS-19(SHR). Depositions of collagen I and fibronectin were also greater in LV tissue of SS compared with SS-19(SHR). CONCLUSION: Our findings point to a link between hypercholesterolemia and LV fibrosis in salt-sensitive hypertension of SS rats which is genetically modulated by RNO19.



Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SS-Chr 19SHR/RkbRatdecreased circulating cholesterol level  IMP compared to SS/RkbRGD 
SS-Chr 19SHR/RkbRatdecreased heart left ventricle weight  IMP compared to SS/JrRkbRGD 
SS-Chr 19SHR/RkbRatdecreased systemic arterial systolic blood pressure  IMP compared to SS/JrRkbRGD 
SS/JrRkbRatperivascular fibrosis  IMP compared to SS-Chr 19SHR/RkbRGD 
Objects Annotated

Strains
SS-Chr 19SHR/Rkb  (NA)
SS/JrRkb  (NA)

Objects referenced in this article
QTL Cm12 Cardiac mass QTL 12 Rattus norvegicus
Strain SHR/FubRkb null Rattus norvegicus

Additional Information