RGD Reference Report - The angiotensin type 1 receptor antagonist, eprosartan, attenuates the progression of renal disease in spontaneously hypertensive stroke-prone rats with accelerated hypertension. - Rat Genome Database

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The angiotensin type 1 receptor antagonist, eprosartan, attenuates the progression of renal disease in spontaneously hypertensive stroke-prone rats with accelerated hypertension.

Authors: Abrahamsen, Christian T  Barone, Frank C  Campbell, Wallace G  Nelson, Allen H  Contino, Lisa C  Pullen, Mark A  Grygielko, Eugene T  Edwards, Richard M  Laping, Nicholas J  Brooks, David P 
Citation: Abrahamsen CT, etal., J Pharmacol Exp Ther. 2002 Apr;301(1):21-8. doi: 10.1124/jpet.301.1.21.
RGD ID: 28912746
Pubmed: PMID:11907153   (View Abstract at PubMed)
DOI: DOI:10.1124/jpet.301.1.21   (Journal Full-text)

The effects of the angiotensin type 1 (AT(1)) receptor antagonist, eprosartan, were studied in a model of severe, chronic hypertension. Treatment of male spontaneously hypertensive stroke prone rats (SHR-SP) fed a high-fat, high-salt diet with eprosartan (60 mg/kg/day i.p.) for 12 weeks resulted in a lowering of blood pressure (250 +/- 9 versus 284 +/- 8 mm Hg), renal expression of transforming growth factor-beta mRNA (1.5 +/- 0.2 versus 5.4 +/- 1.4) and the matrix components: plasminogen activator inhibitor-1 (5.2 +/- 1.4 versus 31.4 +/- 10.7), fibronectin (2.2 +/- 0.6 versus 8.2 +/- 2.2), collagen I-alpha 1 (5.6 +/- 2.0 versus 23.8 +/- 7.3), and collagen III (2.7 +/- 0.9 versus 7.6 +/- 2.1). Data were corrected for rpL32 mRNA expression and expressed relative to Wistar Kyoto (WKY) rats [=1.0]. Expression of fibronectin protein was also lowered by eprosartan (0.8 +/- 0.1 versus 1.9 +/- 0.5), relative to WKY rats. Eprosartan provided significant renoprotection to SHR-SP rats as measured by decreased proteinuria (22 +/- 2 versus 127 +/- 13 mg/day) and histological evidence of active renal damage (5 +/- 2 versus 195 +/- 6) and renal fibrosis (5.9 +/- 0.7 versus 16.4 +/- 1.9) in vehicle- versus eprosartan-treated rats, respectively. Our results demonstrated that AT(1) receptor blockade with eprosartan can reduce blood pressure and preserve renal structure and function in this model of severe, chronic hypertension. These effects were accompanied by a decreased renal expression of transforming growth factor-beta1, plasminogen activator inhibitor-1, and several other extracellular matrix proteins compared with vehicle-treated SHR-SP.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FN1Humanhypertension  ISOFn1 (Rattus norvegicus)mRNA:increased expression:kidney (SHRSP/A3N rat)RGD 
Fn1Mousehypertension  ISOFn1 (Rattus norvegicus)mRNA:increased expression:kidney (SHRSP/A3N rat)RGD 
Fn1Rathypertension  IEP mRNA:increased expression:kidney (SHRSP/A3N rat)RGD 
SERPINE1Humanhypertension  ISOSerpine1 (Rattus norvegicus)mRNA:increased expression:kidney (SHRSP/A3N rat)RGD 
SHRSP/A3NRathypertension MODEL: spontaneousIAGP compared to WKY/NRGD 
Serpine1Rathypertension  IEP mRNA:increased expression:kidney (SHRSP/A3N rat)RGD 
Serpine1Mousehypertension  ISOSerpine1 (Rattus norvegicus)mRNA:increased expression:kidney (SHRSP/A3N rat)RGD 
TGFB1Humanhypertension  ISOTgfb1 (Rattus norvegicus)mRNA:increased expression:kidney (SHRSP/A3N rat)RGD 
Tgfb1Rathypertension  IEP mRNA:increased expression:kidney (SHRSP/A3N rat)RGD 
Tgfb1Mousehypertension  ISOTgfb1 (Rattus norvegicus)mRNA:increased expression:kidney (SHRSP/A3N rat)RGD 
WKY/NRathypertension MODEL: controlIAGP compared to SHRSP/A3NRGD 
SHRSP/A3NRatproteinuria treatmentIAGP  RGD 

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
COL1A1Humaneprosartan decreases expression ISOCol1a1 (Rattus norvegicus)eprosartan decreases expression of collagen I-a1 mRNA in high fat high sodium fed SHRSP/A3N rat kidneyRGD 
COL3A1Humaneprosartan decreases expression ISOCol3a1 (Rattus norvegicus)eprosartan decreases expression of collagen III mRNA in high fat high sodium fed SHRSP/A3N rat kidneyRGD 
Col1a1Rateprosartan decreases expression EXP eprosartan decreases expression of collagen I-a1 mRNA in high fat high sodium fed SHRSP/A3N rat kidneyRGD 
Col1a1Mouseeprosartan decreases expression ISOCol1a1 (Rattus norvegicus)eprosartan decreases expression of collagen I-a1 mRNA in high fat high sodium fed SHRSP/A3N rat kidneyRGD 
Col3a1Rateprosartan decreases expression EXP eprosartan decreases expression of collagen III mRNA in high fat high sodium fed SHRSP/A3N rat kidneyRGD 
Col3a1Mouseeprosartan decreases expression ISOCol3a1 (Rattus norvegicus)eprosartan decreases expression of collagen III mRNA in high fat high sodium fed SHRSP/A3N rat kidneyRGD 
FN1Humaneprosartan decreases expression ISOFn1 (Rattus norvegicus)eprosartan decreases expression of fibronectin mRNA in high fat high sodium fed SHRSP/A3N rat kidneyRGD 
Fn1Rateprosartan decreases expression EXP eprosartan decreases expression of fibronectin mRNA in high fat high sodium fed SHRSP/A3N rat kidneyRGD 
Fn1Mouseeprosartan decreases expression ISOFn1 (Rattus norvegicus)eprosartan decreases expression of fibronectin mRNA in high fat high sodium fed SHRSP/A3N rat kidneyRGD 
SERPINE1Humaneprosartan decreases expression ISOSerpine1 (Rattus norvegicus)eprosartan decreases expression of plasminogen activator inhibitor -1 mRNA in high fat high sodium fed SHRSP/A3N rat kidneyRGD 
Serpine1Rateprosartan decreases expression EXP eprosartan decreases expression of plasminogen activator inhibitor -1 mRNA in high fat high sodium fed SHRSP/A3N rat kidneyRGD 
Serpine1Mouseeprosartan decreases expression ISOSerpine1 (Rattus norvegicus)eprosartan decreases expression of plasminogen activator inhibitor -1 mRNA in high fat high sodium fed SHRSP/A3N rat kidneyRGD 
TGFB1Humaneprosartan decreases expression ISOTgfb1 (Rattus norvegicus)eprosartan decreases expression of TGFbeta mRNA in high fat high sodium fed SHRSP/A3N rat kidneyRGD 
Tgfb1Rateprosartan decreases expression EXP eprosartan decreases expression of TGFbeta mRNA in high fat high sodium fed SHRSP/A3N rat kidneyRGD 
Tgfb1Mouseeprosartan decreases expression ISOTgfb1 (Rattus norvegicus)eprosartan decreases expression of TGFbeta mRNA in high fat high sodium fed SHRSP/A3N rat kidneyRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SHRSP/A3NRatglomerulosclerosis  IAGP compared to WKY/NRGD 
SHRSP/A3NRatincreased systemic arterial systolic blood pressure  IAGP compared to WKY/NRGD 
SHRSP/A3NRatrenal cast  IAGP compared to WKY/NRGD 
SHRSP/A3NRatrenal fibrosis  IAGP compared to WKY/NRGD 
SHRSP/A3NRatrenal interstitial fibrosis  IAGP compared to WKY/NRGD 
SHRSP/A3NRatrenal ischemia  IAGP compared to WKY/NRGD 

Objects Annotated

Genes (Rattus norvegicus)
Col1a1  (collagen type I alpha 1 chain)
Col3a1  (collagen type III alpha 1 chain)
Fn1  (fibronectin 1)
Serpine1  (serpin family E member 1)
Tgfb1  (transforming growth factor, beta 1)

Genes (Mus musculus)
Col1a1  (collagen, type I, alpha 1)
Col3a1  (collagen, type III, alpha 1)
Fn1  (fibronectin 1)
Serpine1  (serine (or cysteine) peptidase inhibitor, clade E, member 1)
Tgfb1  (transforming growth factor, beta 1)

Genes (Homo sapiens)
COL1A1  (collagen type I alpha 1 chain)
COL3A1  (collagen type III alpha 1 chain)
FN1  (fibronectin 1)
SERPINE1  (serpin family E member 1)
TGFB1  (transforming growth factor beta 1)

Strains
SHRSP/A3N  (NA)
WKY/N  (NA)


Additional Information