Long-Term Low Intensity Physical Exercise Attenuates Heart Failure Development in Aging Spontaneously Hypertensive Rats

Pagan, Luana Urbano; Damatto, Ricardo Luiz; Cezar, M. D. M.; Lima, A. R. R.; Bonomo, Camila; Campos, Dijon Henrique Salomé de; Gomes, Mariana Janini; Martinez, Paula Felippe; Oliveira, S. A.; Gimenes, Rodrigo; Rosa, Carlos J. P.; Guizoni, Daniele M.; Moukbel, Yasmin C.; Cicogna, Antônio Carlos; Okoshi, Marina Politi; Okoshi, Katashi

doi:10.1159/000374053

Cited by 62 publications

(97 citation statements)

References 59 publications

(77 reference statements)

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“…Sections (5 µm thick) were stained with hematoxylin–eosin and collagen-specific stain picrosirius red (Sirius red F3BA in aqueous saturated picric acid) [46]. In at least 50 myocytes from each LV, where the nucleus could clearly be identified, the smallest transverse diameters were measured [47]. On average, 20 microscopic fields were used to quantify interstitial collagen fraction.…”

Section: Methodsmentioning

confidence: 99%

Apocynin influence on oxidative stress and cardiac remodeling of spontaneously hypertensive rats with diabetes mellitus

Rosa¹,

Gimenes²,

Campos³

et al. 2016

Cardiovasc Diabetol

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PurposeAlthough increased oxidative stress is a major component of diabetic hypertensive cardiomyopathy, research into the effects of antioxidants on cardiac remodeling remains scarce. The actions of antioxidant apocynin include inhibiting reactive oxygen species (ROS) generation by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and ROS scavenging. We evaluated the effects of apocynin on cardiac remodeling in spontaneously hypertensive rats (SHR) with diabetes mellitus (DM).MethodsMale SHR were divided into four groups: control (SHR, n = 16); SHR treated with apocynin (SHR-APO; 16 mg/kg/day, added to drinking water; n = 16); diabetic SHR (SHR-DM, n = 13); and SHR-DM treated with apocynin (SHR-DM-APO, n = 14), for eight weeks. DM was induced by streptozotocin (40 mg/kg, single dose). Statistical analyzes: ANOVA and Tukey or Mann–Whitney.ResultsEchocardiogram in diabetic groups showed higher left ventricular and left atrium diameters indexed for body weight, and higher isovolumetric relaxation time than normoglycemic rats; systolic function did not differ between groups. Isolated papillary muscle showed impaired contractile and relaxation function in diabetic groups. Developed tension was lower in SHR-APO than SHR. Myocardial hydroxyproline concentration was higher in SHR-DM than SHR, interstitial collagen fraction was higher in SHR-DM-APO than SHR-APO, and type III collagen protein expression was lower in SHR-DM and SHR-DM-APO than their controls. Type I collagen and lysyl oxidase expression did not differ between groups. Apocynin did not change collagen tissue. Myocardial lipid hydroperoxide concentration was higher in SHR-DM than SHR and SHR-DM-APO. Glutathione peroxidase activity was lower and catalase higher in SHR-DM than SHR. Apocynin attenuated antioxidant enzyme activity changes in SHR-DM-APO. Advanced glycation end-products and NADPH oxidase activity did not differ between groups.ConclusionApocynin reduces oxidative stress independently of NADPH oxidase activity and does not change ventricular or myocardial function in spontaneously hypertensive rats with diabetes mellitus. The apocynin-induced myocardial functional impairment in SHR shows that apocynin actions need to be clarified during sustained chronic pressure overload.

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Section: Methodsmentioning

confidence: 99%

Apocynin influence on oxidative stress and cardiac remodeling of spontaneously hypertensive rats with diabetes mellitus

Rosa¹,

Gimenes²,

Campos³

et al. 2016

Cardiovasc Diabetol

View full text Add to dashboard Cite

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“…For example, the body surface of the individual participant may affect the lumen diameters of the coronary artery, and this could be easily determined if the coronary artery diameters were adjusted for body surface area. In addition, many therapies such as medications and kinesitherapy may affect the diameters of the coronary arteries and cardiac function [24, 25], and it would be optimal if we had obtained the data regarding the medications regularly taken by the included participants. Subsequent adjustment for medication use might minimize the potential confounding effect from the treatment.…”

Section: Limitationsmentioning

confidence: 99%

Coronary Artery Diameter is Inversely Associated with the Severity of Coronary Lesions in Patients Undergoing Coronary Angiography

Zhou¹,

Liu²,

Ge³

et al. 2017

Cell Physiol Biochem

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Background: The diameters of the coronary arteries have been suggested to be a potential predictor of coronary artery disease (CAD). However, whether the diameters of the coronary arteries are associated with the coronary lesion severity on angiography has not been determined. Methods: One hundred sixty-seven consecutive adult patients (109 men and 58 women) aged 31–84 years who underwent coronary angiography for suspected or known CAD were enrolled. The known catheter tip diameter was used as the calibration to measure the diameters of coronary arteries, and the severity of coronary lesions was evaluated with the vessel score and Gensini score. Results: In patients with a higher vessel score and Gensini score, the diameters of the left main (LM), left anterior descending (LAD), left circumflex (LCX), and right coronary arteries (RCA) were smaller (all p<0.05) than those in patients with lower scores. Multiple linear regression analysis indicated that the average coronary artery diameter was significantly associated with the Gensini score (β=-0.444, p<0.00001). Moreover, the diameters of the coronary arteries were potential predictors of CAD, with areas under the receiver operating characteristic curves of 0.268 for average diameter (95% confidence interval [CI]: 0.183–0.353, p<0.00001), 0.356 for the LM diameter (95% CI: 0.266–0.445, p=0.005), 0.214 for the LAD diameter (95% CI: 0.136–0.291, p<0.00001), 0.366 for the LCX diameter (95% CI: 0.271–0.461, p=0.009), and 0.346 for the RCA diameter (95% CI: 0.245–0.447, p=0.003). Conclusion: The diameters of coronary arteries are inversely associated with the severity of CAD.

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“…Finally, it has been found that cardiac function varies with age in SHR rats [28,29], and the reason we chose 36-week-old SHR rats in our study is that the cardiac functions in SHR rats at this age simulated those of elderly hypertensive patients, i.e., chronic hypertension in this age group of patients has led to left ventricular hypertrophy and diastolic dysfunction [30,31].The blood pressure of SHR rats starts to rise at 6-8 weeks after birth; compensatory ventricular hypertrophy starts to develop at 16-18 weeks after birth; diastolic dysfunction begins to appear at about 36 weeks after birth, while systolic function remains in the normal range; and decompensated ventricular hypertrophy started to develop at 70 weeks after birth, with significant dilation of the ventricular cavity and significant decrease of systolic and diastolic function.…”

Section: Discussionmentioning

confidence: 95%

Amlodipine and Atorvastatin Improved Hypertensive Cardiac Remodeling through Regulation of MMPs/TIMPs in SHR Rats

Hao²,

Du³

et al. 2016

Cell Physiol Biochem

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Background: MMPs/TIMPs system is well known to play important roles in pressure overload-induced cardiac remodeling, and Amlodipine and Atorvastatin have been showed to exert favourable protective effects on cardiovascular disease, however, it is not clear whether Amlodipine and Atorvastatin can improve hypertensive cardiac remodeling and whether the MMPs/TIMPs system is involved. The present study aims to answer these questions. Methods: 36 weeks old male spontaneous hypertension (SHR) rats were randomly divided into four groups: 1). SHR control group, 2). Amlodipine alone (10 mg/kg/d) group, 3). Atorvastatin alone (10 mg/kg/d) group, 4).Combination of Amlodipine and Atorvastatin (10 mg/kg/d for each) group. Same gender, weight and age of Wistar-Kyoto (WKY) rats with normal blood pressure were used as normal control. Drugs were administered by oral gavage over 12 weeks. The blood pressure and left ventricle mass index were measured. Enzyme activity of MMP-2 and MMP-9 was assessed with Gelatin zymography. MMP-2, MMP-9, TIMP-1 and TIMP-2 mRNA and protein expression was studied by RT-PCR and Western blot. Single factor ANOVA and LSD-t test were used in statistical analysis. Results: Treatment with Amlodipine alone or combination with atorvastatin significantly decreased blood pressure, left ventricle mass index in SHR rats (P < 0.05 for both). Compared with WKY rats, the myocardial levels of MMP-2, MMP-9 mRNA, protein and enzyme activity were significantly increased (P<0.05). Amlodipine alone, Atorvastatin alone, and combination of the two all reduced MMP-2 and MMP-9 mRNA, protein and enzyme activity, with the best effects seen in the combination. Compared with WKY rats, the myocardial levels of TIMP-1 mRNA and protein were significantly increased (P<0.05), however, there was no difference in levels of TIMP-2. Neither Amlodipine alone, Atorvastatin alone, nor combination of the two drugs significantly affect the expression of TIMP-1 or TIMP-2. Conclusion: Amlodipine and Atorvastatin could improve ventricular remodeling in SHR rats through intervention with the imbalance of MMP-2/TIMP-2 and MMP-9/TIMP-1 system.

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Long-Term Low Intensity Physical Exercise Attenuates Heart Failure Development in Aging Spontaneously Hypertensive Rats

Cited by 62 publications

References 59 publications

Apocynin influence on oxidative stress and cardiac remodeling of spontaneously hypertensive rats with diabetes mellitus

Apocynin influence on oxidative stress and cardiac remodeling of spontaneously hypertensive rats with diabetes mellitus

Coronary Artery Diameter is Inversely Associated with the Severity of Coronary Lesions in Patients Undergoing Coronary Angiography

Amlodipine and Atorvastatin Improved Hypertensive Cardiac Remodeling through Regulation of MMPs/TIMPs in SHR Rats

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