RGD Reference Report - Renoprotective effects of carvedilol in hypertensive-stroke prone rats may involve inhibition of TGF beta expression. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Renoprotective effects of carvedilol in hypertensive-stroke prone rats may involve inhibition of TGF beta expression.

Authors: Wong, V Y  Laping, N J  Nelson, A H  Contino, L C  Olson, B A  Gygielko, E  Campbell, W G  Barone, F  Brooks, D P 
Citation: Wong VY, etal., Br J Pharmacol. 2001 Nov;134(5):977-84. doi: 10.1038/sj.bjp.0704329.
RGD ID: 30296650
Pubmed: (View Article at PubMed) PMID:11682445
DOI: Full-text: DOI:10.1038/sj.bjp.0704329

1. The effect of carvedilol on renal function, structure and expression of TGF beta and the matrix proteins fibronectin, collagen I and collagen III, was evaluated in spontaneously hypertensive stroke-prone (SHR-SP) rats fed a high fat, high salt diet. 2. Carvedilol treatment for 11 to 18 weeks did not alter systolic blood pressure in SHR-SP rats, however, it resulted in a significant reduction in heart rate. 3. Carvedilol treatment reduced renal fibrosis and total, active and chronic renal damage to levels approaching those of WKY rats on a normal diet. 4. Urinary protein excretion was higher in SHR-SP rats (51+/-10 mg day(-1)) than WKY rats (18+/-2 mg day(-1)) and this was further increased when SHR-SP rats were fed a high fat, high salt diet (251+/-120 mg day(-1)). Treatment with carvedilol resulted in significantly lower urinary protein excretion (37+/-15 mg day(-1)). 5. The expression of TGF beta mRNA was significantly higher in SHR-SP rats compared to WKY rats and a further increase was observed when rats were fed a high fat, high salt diet. Renal TGF beta expression was significantly reduced by treatment with carvedilol. The expression of fibronectin and collagen I and collagen III mRNA showed a pattern similar to that observed with TGF beta mRNA expression. Collagen I mRNA expression followed a pattern similar to renal fibrosis. 6. These data indicate that carvedilol can provide significant renal protection in the absence of any antihypertensive activity and that the mechanisms involved in this action may include reduced expression of profibrotic factors such as TGF beta.

Annotation

Disease Annotations    
hypertension  (IAGP,ISO)
proteinuria  (IAGP)

Gene-Chemical Interaction Annotations    
carvedilol  (EXP,ISO)

Phenotype Annotations    

Mammalian Phenotype
Phenotype Values via PhenoMiner

View PhenoMiner data from this reference here 

Objects Annotated

Genes (Rattus norvegicus)
Col1a1  (collagen type I alpha 1 chain)
Col3a1  (collagen type III alpha 1 chain)
Fn1  (fibronectin 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)
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)
TGFB1  (transforming growth factor beta 1)

Strains
SHRSP/A3N  (NA)
WKY/N  (NA)


Additional Information