RGD Reference Report - Cardioprotective mechanism of telmisartan via PPAR-gamma-eNOS pathway in dahl salt-sensitive hypertensive rats. - Rat Genome Database

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Cardioprotective mechanism of telmisartan via PPAR-gamma-eNOS pathway in dahl salt-sensitive hypertensive rats.

Authors: Kobayashi, N  Ohno, T  Yoshida, K  Fukushima, H  Mamada, Y  Nomura, M  Hirata, H  Machida, Y  Shinoda, M  Suzuki, N  Matsuoka, H 
Citation: Kobayashi N, etal., Am J Hypertens. 2008 May;21(5):576-81. Epub 2008 Mar 20.
RGD ID: 2301888
Pubmed: PMID:18437150   (View Abstract at PubMed)
DOI: DOI:10.1038/ajh.2008.27   (Journal Full-text)

BACKGROUND: Recently, some investigators have shown that telmisartan, an angiotensin II (Ang II)-receptor blocker (ARB), is a partial agonist of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma). We investigate whether telmisartan improves cardiovascular remodeling associated with the production of endothelial nitric oxide synthase (eNOS) through PPAR-gamma, inhibits the Rho-kinase pathway, and suppresses oxidative stress in Dahl salt-sensitive (DS) hypertensive rats. METHODS: Telmisartan (1 mg/kg per day) or telmisartan plus PPAR-gamma inhibitor, GW9662 (1 mg/kg per day) was administered from the age of 6-11 weeks. Age-matched male Dahl salt-resistant (DR) rats served as a control group. RESULTS: The levels of eNOS and PPAR-gamma expression, and eNOS phosphorylation were significantly lower in DS rats than in DR rats. Chronic telmisartan treatment in DS rats significantly increased these parameters, but not telmisartan plus GW9662. Telmisartan effectively inhibited the vascular lesion formation such as medial thickness and perivascular fibrosis, but not telmisartan plus GW9662. Moreover, upregulated RhoA protein, Rho-kinase mRNA, and myosin light-chain phosphorylation in DS rats was decreased by telmisartan to a similar degree as observed after treatment with Y-27632, a selective Rho-kinase inhibitor. In addition, NAD(P)H oxidase p22phox, p47phox, gp91phox expression, and mitogen-activated protein kinase and its downstream effector p70 S6 kinase phosphorylation in DS rats was also inhibited by telmisartan. CONCLUSIONS: These results suggest that the cardioprotective mechanism of telmisartan may be partly due to improvement of endothelial function associated with PPAR-gamma-eNOS, oxidative stress, and Rho-kinase pathway.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PPARGHumanhypertension  ISOPparg (Rattus norvegicus) RGD 
PpargRathypertension  IMP  RGD 
PpargMousehypertension  ISOPparg (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pparg  (peroxisome proliferator-activated receptor gamma)

Genes (Mus musculus)
Pparg  (peroxisome proliferator activated receptor gamma)

Genes (Homo sapiens)
PPARG  (peroxisome proliferator activated receptor gamma)


Additional Information