AT1 Receptor Blockade Attenuates Insulin Resistance and Myocardial Remodeling in Rats with Diet-Induced Obesity

Oliveira, S. A.; Martinez, Paula Felippe; Guizoni, Danielle M.; Campos, Dijon; Fernandes, Tiago Lazzaretti; Oliveira, Edilamar Menezes de; Okoshi, Marina Politi; Okoshi, Katashi; Padovani, Carlos Roberto; Cicogna, Antônio Carlos

doi:10.1371/journal.pone.0086447

Cited by 46 publications

(49 citation statements)

References 51 publications

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“…Moreover, studies have shown that angiotensin II can decrease insulin sensitivity and induce insulin resistance [35]. After binding to the AT1 receptor, the AT1 receptor autoantibody exerts angiotensin II-like effects involving insulin resistance [36].…”

Section: Discussionmentioning

confidence: 99%

Autoantibodies against β1 Receptor and AT1 Receptor in Type 2 Diabetes Patients with Left Ventricular Dilatation

Zhao

2014

Cardiology

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Objectives: To explore the relationship between the autoantibodies against the β1 and AT1 receptors and left ventricular dilatation in patients with type 2 diabetes (T2DM). Methods: The autoantibodies against the β1 and angiotensin II type 1 (AT1) receptors of T2DM patients with and without hypertension were screened by ELISA. Multiple logistic regression was used to analyze the risk factors for left ventricular dilatation. The reversing effect of left ventricular dilatation was evaluated after receptor blocker treatment. Results: The positive rates of autoantibodies against the β1 and AT1 receptors (43.0 and 44.1%, respectively) in T2DM patients with hypertension were significantly higher than those in normotensive patients (16.0 and 10.4%, respectively; all p < 0.01). Furthermore, among T2DM patients with hypertension, the positive rates (61.4 and 64.9%, respectively) in patients with left ventricular dilatation were remarkably higher than those with normal left ventricular dimensions (34.4 and 36.1%, respectively; all p < 0.01). The presence of β1 receptor antibody and AT1 receptor antibody were risk factors for left ventricular dilatation (p < 0.05). The curative effect of metoprolol tartrate and valsartan in reversing left ventricular hypertrophy in the group positive for autoantibodies was much better than in the negative group. Conclusion: The findings show that autoantibodies against the β1 and AT1 receptors may play a role in predicting left ventricular dilatation in T2DM patients in combination with hypertension. Metoprolol tartrate and valsartan are effective and safe in the treatment of these patients.

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Section: Discussionmentioning

confidence: 99%

Autoantibodies against β1 Receptor and AT1 Receptor in Type 2 Diabetes Patients with Left Ventricular Dilatation

Zhao

2014

Cardiology

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“…Echocardiogram was performed before and after NAC treatment (Vivid S6, General Electric Medical Systems, Tirat Carmel, Israel) using a 5 to 11.5 MHz electronic transducer, according to a previously described method [26,27,28,29]. …”

Section: Methodsmentioning

confidence: 99%

Influence of N-Acetylcysteine on Oxidative Stress in Slow-Twitch Soleus Muscle of Heart Failure Rats

Martinez

Bonomo

Guizoni

et al. 2015

Cell Physiol Biochem

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Background: Chronic heart failure is characterized by decreased exercise capacity with early exacerbation of fatigue and dyspnea. Intrinsic skeletal muscle abnormalities can play a role in exercise intolerance. Causal or contributing factors responsible for muscle alterations have not been completely defined. This study evaluated skeletal muscle oxidative stress and NADPH oxidase activity in rats with myocardial infarction (MI) induced heart failure. Methods and Results: Four months after MI, rats were assigned to Sham, MI-C (without treatment), and MI-NAC (treated with N-acetylcysteine) groups. Two months later, echocardiogram showed left ventricular dysfunction in MI-C; NAC attenuated diastolic dysfunction. In soleus muscle, glutathione peroxidase and superoxide dismutase activity was decreased in MI-C and unchanged by NAC. 3-nitrotyrosine was similar in MI-C and Sham, and lower in MI-NAC than MI-C. Total reactive oxygen species (ROS) production was assessed by HPLC analysis of dihydroethidium (DHE) oxidation fluorescent products. The 2-hydroxyethidium (EOH)/DHE ratio did not differ between Sham and MI-C and was higher in MI-NAC. The ethidium/DHE ratio was higher in MI-C than Sham and unchanged by NAC. NADPH oxidase activity was similar in Sham and MI-C and lower in MI-NAC. Gene expression of p47^phox was lower in MI-C than Sham. NAC decreased NOX4 and p22^phox expression. Conclusions: We corroborate the case that oxidative stress is increased in skeletal muscle of heart failure rats and show for the first time that oxidative stress is not related to increased NADPH oxidase activity.

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“…Pathological cardiac hypertrophy and dysfunction associated with metabolic disorders have been reported in obesity [4,5,6]. The obese Zucker rat (OZR), a genetic model of morbid obesity, presents many of the same cardiovascular deficits noted in obese humans including myocardial hypertrophy [5,7], cardiac microvascular rarefaction [8], and exercise intolerance [5,9].…”

Section: Introductionmentioning

confidence: 99%

Exercise Training Restores the Cardiac Microrna-16 Levels Preventing Microvascular Rarefaction in Obese Zucker Rats

et al. 2018

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Objective: To evaluate the effects of aerobic exercise training (AET) on cardiac miRNA-16 levels and its target gene VEGF related to microvascular rarefaction in obese Zucker rats (OZR). Methods: OZR (n = 11) and lean (L; n = 10) male rats were assigned into 4 groups: OZR, trained OZR (OZRT), L and trained L (LT). Swimming exercise training lasted 60 min, 1×/day/10 weeks, with 4% body weight workload. Cardiac angiogenesis was assessed by histological analysis (periodic acid-Schiff) by calculating the capillary/fiber ratio. The protein expressions of VEGF, VEGFR2, and CD31 were evaluated by western blot. The expression of miRNA-16 was evaluated by real-time PCR. Results: Heart rate decreased in the trained groups compared to sedentary groups. The cardiac capillary/fiber ratio was reduced in OZR compared to L, LT and OZRT groups, indicating that aerobic exercise training (AET) was capable of reversing the microvascular rarefaction in the obese animals. miRNA-16 expression was increased in OZR compared to L, LT and OZRT. In contrast, its target, VEGF protein expression was 24% lower in OZR compared to L group, which has been normalized in OZRT group. VEGFR2 protein expression was increased in trained groups compared to their controls. CD31, a endothelial cells marker, showed increased expression in OZRT compared to OZR, indicating greater vascularization in OZRT group. Conclusion: AET induced cardiac angiogenesis in obese animals. This revascularization is associated with a decrease in miRNA-16 expression permissive for increased VEGF protein expression, suggesting a mechanism for potential therapeutic application in vascular diseases.

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AT1 Receptor Blockade Attenuates Insulin Resistance and Myocardial Remodeling in Rats with Diet-Induced Obesity

Cited by 46 publications

References 51 publications

Autoantibodies against β1 Receptor and AT1 Receptor in Type 2 Diabetes Patients with Left Ventricular Dilatation

Autoantibodies against β1 Receptor and AT1 Receptor in Type 2 Diabetes Patients with Left Ventricular Dilatation

Influence of N-Acetylcysteine on Oxidative Stress in Slow-Twitch Soleus Muscle of Heart Failure Rats

Exercise Training Restores the Cardiac Microrna-16 Levels Preventing Microvascular Rarefaction in Obese Zucker Rats

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