Cardioprotective Mechanism of Telmisartan via PPAR- -eNOS Pathway in Dahl Salt-Sensitive Hypertensive Rats

Kobayashi, Noboru; Ohno, Tomoyuki; Yoshida, Kohtaro; Fukushima, Hiromichi; Mamada, Yasuko; Nomura, Mika; Hirata, Hirokuni; Machida, Yoshifumi; Shinoda, Motoo; Suzuki, Noriko; Matsuoka, Hiroaki

doi:10.1038/ajh.2008.27

Cited by 94 publications

(77 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…33 Recently, it has been reported that telmisartan ameliorated cardiac remodeling in DSsensitive hypertensive rats through PPAR-g-endothelial nitric oxide synthase pathway. 34 Although Takano et al 35 reported that PPAR-g was expressed in neonatal normal cardiac myocytes, in this study, immunohistochemical results have shown that only marginal or trivial immunoreactivity for PPAR-g was detected in myocardium of normal rats. Interestingly, we also observed increased expression of PPAR-g in rats with DCM in line with the previous reports 29,36,37 and these changes were significantly decreased by telmisartan treatment ( Figures 1c, d, 2a and a1).…”

Section: Discussioncontrasting

confidence: 56%

Telmisartan, an angiotensin-II receptor blocker ameliorates cardiac remodeling in rats with dilated cardiomyopathy

et al. 2010

View full text Add to dashboard Cite

Multiple trials over the past several years have examined indications for angiotensin receptor blockers (ARBs) in the treatment of left ventricular (LV) dysfunction, both acutely after myocardial infarction and in chronic heart failure (CHF). However, the effects of telmisartan, an ARB in rats with CHF after experimental autoimmune myocarditis (EAM) have not yet been analyzed. CHF was elicited in Lewis rats by immunization with cardiac myosin, and 28 days after immunization, the surviving Lewis rats were divided into two groups and treated with either telmisartan (10 mg kg -1 day -1 ) or vehicle. After 4 weeks of treatment, we analyzed the effects of telmisartan on cardiac function, proinflammatory cytokines and cardiac remodeling in EAM rats. Myocardial functional parameters measured by hemodynamic and echocardiographic studies were significantly improved by telmisartan treatment in rats with CHF compared with those of vehicle-treated rats with CHF. Telmisartan significantly reduced levels of cardiac fibrosis, hypertrophy and its marker molecules (LV mRNA expressions of transforming growth factor beta 1, collagen I and III, and atrial natriuretic peptide), and peroxisome proliferator-activated receptor-c protein expression compared with those of vehicle-treated rats. CHF-induced increases in myocardial mRNA expressions of proinflammatory cytokines, (interleukin (IL)-6, IL-1b), monocyte chemoattractant protein-1 and matrix metalloproteinases (MMP-2 and -9) were also suppressed by the treatment with telmisartan. Moreover, the plasma level of angiotensin-II was significantly elevated in telmisartan-treated rats. Our results indicate that telmisartan treatment significantly improved LV function and ameliorated the progression of cardiac remodeling in rats with CHF after EAM.

show abstract

Section: Discussioncontrasting

confidence: 56%

Telmisartan, an angiotensin-II receptor blocker ameliorates cardiac remodeling in rats with dilated cardiomyopathy

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Independent of AT1 receptor-blocking activity, telmisartan is responsible for the additional antioxidant and anti-inflammatory activities. The drug acts as a partial agonist of PPAR-g. 14,15,35,36 Activation of PPAR-g induces catalase gene expression and inhibits nuclear factor-kB, thus, combating oxidative stress and downregulating most of the proinflammatory responses. 37,38 Another possible mechanism is that telmisartan, by blocking AT1 receptor, allows Ang-II to interact more with the Ang-II type-2 receptor (AT 2 ) which, on the contrary, provides cellular protective action against oxidative stress and excitotoxic damage.…”

Section: Discussionmentioning

confidence: 99%

Role of fenofibrate alone and in combination with telmisartan on renal ischemia/reperfusion injury

et al. 2010

View full text Add to dashboard Cite

It was demonstrated that fenofibrate and telmisartan exerted renoprotective effects in ischemia/reperfusion (I/R) injury. Because the combination of fenofibrate and telmisartan synergistically enhanced peroxisome proliferator-activated receptor (PPAR) activation, we hypothesized that the combination of both drugs may exert prolonged beneficial effects in renal I/R injury than fenofibrate alone. Forty-eight male Wistar albino rats were divided into eight groups. Hyperlipidemia was induced by cholesterol feeding for 4 weeks. At the end of the fourth week, renal I/R injury was performed by occlusion of both renal vascular pedicles for 60 minutes, followed by 24 hours of reperfusion. In the treatment group, fenofibrate alone and in combination with telmisartan was administered 2 weeks prior to renal ischemia. At the end of the experiment, blood and kidneys were isolated for biochemical and histological analysis. I/R in hyperlipidemic rat shows significantly increased lipid peroxidation, nitric oxide, and myeloperoxidase activity, and depletion of antioxidant enzyme compared with control rats, and that was significantly restored after fenofibrate and telmisartan treatment. Also, significant increases in serum homocysteine level were detected following I/R. Fenofibrate treatment further elevated homocysteine level, which was reduced by telmisartan in combination with fenofibrate. The most significant histological damage was found in the hyperlipidemic rat subjected to renal I/R, which was reduced significantly with combination therapy. The results of this study concluded that fenofibrate alone and in combination with telmisartan significantly ameliorated renal I/R injury. The additive beneficial effect of telmisartan is predicted to reduce homocysteine-induced oxidative stress through reduced nitric oxide production during I/R.

show abstract

“…p38 MAPK and myosin phosphatase targeting subunit (MYPT-1) phosphorylation was measured as described in detail previously [20][21][22][23] .…”

Section: P38 Mapk and Mypt-1 Phosphorylationmentioning

confidence: 99%

“…Histological detection of superoxide anion in the LV was performed using dihydroethidium (DHE) as described previously 18,19,21,23) .…”

Section: Detection Of Superoxide Anion In the LVmentioning

confidence: 99%

See 1 more Smart Citation

Cardioprotective Effect of a Combination of Rho-Kinase Inhibitor and P38 MAPK Inhibitor on Cardiovascular Remodeling and Oxidative Stress in Dahl Rats

Takeshima

Kobayashi

Koguchi

et al. 2012

JAT

View full text Add to dashboard Cite

Aim: Rho-kinase plays a critical role in various cellular functions. p38 mitogen-activated protein kinase (p38 MAPK) plays a central role in the inflammatory cytokine response to immune challenge. We evaluated the effects of a combination of fasudil, a Rho-kinase inhibitor, and FR167653, a p38 MAPK inhibitor, on cardiovascular remodeling, inflammation, and oxidative stress in Dahl salt-sensitive hypertensive (DS) rats. Methods: DS and Dahl salt-resistant (DR) rats were fed a high-salt diet at 6 weeks of age. Vehicle, fasudil (100 mg/kg per day), FR167653 (2 mg/kg per day), and a combination of fasudil and FR167653 were administered to 6-week-old DS rats for 5 weeks.

show abstract

Cardioprotective Mechanism of Telmisartan via PPAR- -eNOS Pathway in Dahl Salt-Sensitive Hypertensive Rats

Abstract: 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.

Cited by 94 publications

References 22 publications

Telmisartan, an angiotensin-II receptor blocker ameliorates cardiac remodeling in rats with dilated cardiomyopathy

Telmisartan, an angiotensin-II receptor blocker ameliorates cardiac remodeling in rats with dilated cardiomyopathy

Role of fenofibrate alone and in combination with telmisartan on renal ischemia/reperfusion injury

Cardioprotective Effect of a Combination of Rho-Kinase Inhibitor and P38 MAPK Inhibitor on Cardiovascular Remodeling and Oxidative Stress in Dahl Rats

Contact Info

Product

Resources

About