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Cardioprotective mechanism of telmisartan via PPAR-gamma-eNOS pathway in dahl salt-sensitive hypertensive rats.
Am J Hypertens. 2008 May; 21(5):576-81.AJ

Abstract

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.

Authors+Show Affiliations

Department of Hypertension and Cardiorenal Medicine, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan. nao-koba@dokkyomed.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18437150

Citation

Kobayashi, Naohiko, et al. "Cardioprotective Mechanism of Telmisartan Via PPAR-gamma-eNOS Pathway in Dahl Salt-sensitive Hypertensive Rats." American Journal of Hypertension, vol. 21, no. 5, 2008, pp. 576-81.
Kobayashi N, Ohno T, Yoshida K, et al. Cardioprotective mechanism of telmisartan via PPAR-gamma-eNOS pathway in dahl salt-sensitive hypertensive rats. Am J Hypertens. 2008;21(5):576-81.
Kobayashi, N., Ohno, T., Yoshida, K., Fukushima, H., Mamada, Y., Nomura, M., Hirata, H., Machida, Y., Shinoda, M., Suzuki, N., & Matsuoka, H. (2008). Cardioprotective mechanism of telmisartan via PPAR-gamma-eNOS pathway in dahl salt-sensitive hypertensive rats. American Journal of Hypertension, 21(5), 576-81. https://doi.org/10.1038/ajh.2008.27
Kobayashi N, et al. Cardioprotective Mechanism of Telmisartan Via PPAR-gamma-eNOS Pathway in Dahl Salt-sensitive Hypertensive Rats. Am J Hypertens. 2008;21(5):576-81. PubMed PMID: 18437150.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cardioprotective mechanism of telmisartan via PPAR-gamma-eNOS pathway in dahl salt-sensitive hypertensive rats. AU - Kobayashi,Naohiko, AU - Ohno,Tomoyuki, AU - Yoshida,Kohtaro, AU - Fukushima,Hiromichi, AU - Mamada,Yasuko, AU - Nomura,Mika, AU - Hirata,Hisato, AU - Machida,Yoshifumi, AU - Shinoda,Motoo, AU - Suzuki,Noriko, AU - Matsuoka,Hiroaki, Y1 - 2008/03/20/ PY - 2008/4/26/pubmed PY - 2008/6/28/medline PY - 2008/4/26/entrez SP - 576 EP - 81 JF - American journal of hypertension JO - Am J Hypertens VL - 21 IS - 5 N2 - 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. SN - 0895-7061 UR - https://www.unboundmedicine.com/medline/citation/18437150/Cardioprotective_mechanism_of_telmisartan_via_PPAR_gamma_eNOS_pathway_in_dahl_salt_sensitive_hypertensive_rats_ L2 - https://academic.oup.com/ajh/article-lookup/doi/10.1038/ajh.2008.27 DB - PRIME DP - Unbound Medicine ER -