Pioglitazone attenuates cardiac hypertrophy in rats with salt-sensitive hypertension: role of activation of AMP-activated protein kinase and inhibition of Akt

Kato, Mayuko; Shibata, Rei; Okihara, Koji; Miyachi, Masaaki; Yazawa, Hisatoyo; Tsuboi, Koji; Yamada, Takashi; Nishizawa, Tsutomu; Noda, Akiko; Cheng, Xian Wu; Murate, Takashi; Koike, Yasuo; Murohara, Toyoaki; Yokota, Mitsuhiro; Nagata, Kazuya

doi:10.1097/hjh.0b013e328302f0f7

Cited by 50 publications

(39 citation statements)

References 43 publications

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“…Already there is experimental evidence for thioglitazones increasing Akt activity and ameliorating IRI in ischemia/ reperfusion models 131,132 and hypertrophy in pressure overload, 84 whereas rapamycin, targeting mTOR downstream of Akt, reduces cardiac hypertrophy and fibrosis in uremic mice. 88 With proper clinical study, targeting future therapies at these underlying cellular mechanisms of uremic cardiomyopathy may finally start to reduce the burden of uremic cardiomyopathy in the CKD population.…”

Section: Discussionmentioning

confidence: 99%

“…89 Furthermore, in a nonuremic model, chronic hyperinsulinemia produced pathologic hypertrophy and fibrosis by activation of a complex network of intracellular pathways, including Akt, 69 whereas the use of peroxisome proliferator-activated receptor ␥ (PPAR-␥) agonists in models of salt-sensitive hypertension decreased cardiac hypertrophy and fibrosis in association with reduced Akt phosphorylation. 84 Furthermore, as mentioned already, chronic overexpression of Akt1 can produce cardiac fibrosis associated with LVH. 68,71 Thus, although cardiac fibrosis is a feature of the uremic heart, knowledge of the underlying mechanisms is still sparse.…”

Section: Angiogenesismentioning

confidence: 99%

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Uremic Cardiomyopathy and Insulin Resistance

Semple

Smith

Bhandari

et al. 2011

Journal of the American Society of Nephrology

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Section: Discussionmentioning

confidence: 99%

Section: Angiogenesismentioning

confidence: 99%

Uremic Cardiomyopathy and Insulin Resistance

Semple

Smith

Bhandari

et al. 2011

Journal of the American Society of Nephrology

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“…After echocardiography, a 2F micromanometertipped catheter (SPR-407; Millar Instruments, Houston, TX, USA) that had been calibrated relative to atmospheric pressure was inserted through the right carotid artery into the LV. 20 Tracings of LV pressure and the electrocardiogram were digitized to determine LV end-diastolic pressure (LVEDP). The time constant of isovolumic relaxation (tau) was calculated by the derivative method of Raff and Glantz, as described previously.…”

Section: Echocardiographic and Hemodynamic Analysesmentioning

confidence: 99%

Mechanism underlying the efficacy of combination therapy with losartan and hydrochlorothiazide in rats with salt-sensitive hypertension

et al. 2011

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Although thiazide diuretics are commonly used to supplement angiotensin receptor blockers for treatment of hypertension, the mechanism underlying the therapeutic effects of this drug combination remains unclear. We investigated the antihypertensive and cardioprotective effects of combination therapy with losartan (LOS) and hydrochlorothiazide (HCTZ), in comparison with those of either drug alone, in Dahl salt-sensitive hypertensive rats. Rats fed a high-salt diet from 6 weeks of age were treated with LOS, HCTZ, both drugs (COMB) and vehicle from 6 to 11 weeks. The salt-induced increase in systolic blood pressure was attenuated moderately by LOS and to a greater extent by HCTZ and COMB. Left ventricular (LV) hypertrophy and fibrosis, diastolic dysfunction, as well as angiotensin-converting enzyme and angiotensin II type 1A (AT 1A ) receptor gene expression were attenuated similarly by LOS and HCTZ and more so by COMB. LOS downregulated expression of the AT 1A receptor gene, without affecting that of the AT 2 receptor gene, in the aorta. In contrast, neither HCTZ nor COMB affected aortic expression of the AT 1A receptor gene, but both markedly upregulated that of the AT 2 receptor gene. The salt-induced decrease in the plasma concentration of nitric oxide metabolites was attenuated substantially by LOS and abolished by both HCTZ and COMB. In conclusion, the combination of LOS and HCTZ attenuated hypertension, as well as LV remodeling and diastolic dysfunction, more effectively than did LOS or HCTZ alone in rats with salt-sensitive hypertension. Modulation of the cardiac and vascular renin-angiotensin system may have contributed to these beneficial effects of the drug combination.

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“…[89][90][91][92] Chronic administration of pioglitazone to rats with salt-sensitive hypertension attenuates the development of LVH and fibrosis, which is likely to be attributable to stimulation of adiponectin secretion. 93 Therefore, adiponectin may play an essential role in the cardioprotective effects of pioglitazone, but detailed biochemical and genetic studies are required to better understand these effects.…”

Section: Therapeutic Approaches To Increasing Adiponectin Productionmentioning

confidence: 99%

Adiponectin and Cardiovascular Disease

Shibata

Ouchi

Murohara

2009

Circ J

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195

142

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Obesity is strongly associated with metabolic and cardiovascular disorders. Adiponectin is an adipose-derived plasma protein that is downregulated in subjects with obesity-related disorders. Low levels of adiponectin are associated with the increased prevalence of obesity-linked cardiovascular diseases, including ischemic heart disease and peripheral artery disease. Experimental findings have shown that adiponectin has beneficial effects in the cardiovascular system by directly acting on the component cells of the heart and blood vessels. Adiponectin protects cardiovascular tissues under conditions of stress through a number of mechanisms: inhibition of pro-inflammatory and hypertrophic responses, and stimulation of endothelial cell responses. These effects of adiponectin are mainly attributed to the modulation of signaling molecules, including AMP-activated protein kinase. Thus, adiponectin could be a promising therapeutic target for cardiovascular diseases. (Circ J 2009; 73: 608 -614)

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Pioglitazone attenuates cardiac hypertrophy in rats with salt-sensitive hypertension: role of activation of AMP-activated protein kinase and inhibition of Akt

Cited by 50 publications

References 43 publications

Uremic Cardiomyopathy and Insulin Resistance

Uremic Cardiomyopathy and Insulin Resistance

Mechanism underlying the efficacy of combination therapy with losartan and hydrochlorothiazide in rats with salt-sensitive hypertension

Adiponectin and Cardiovascular Disease

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