Low‐intensity aerobic exercise improves cardiac remodelling of adult spontaneously hypertensive rats

Pagan, Luana Urbano; Damatto, Ricardo Luiz; Gomes, Mariana Janini; Lima, A. R. R.; Cezar, M. D. M.; Damatto, F C; Reyes, David Rafael Abreu; Caldonazo, Túlio; Polegato, Bertha Furlan; Okoshi, Marina Politi; Okoshi, Katashi

doi:10.1111/jcmm.14530

Cited by 19 publications

(18 citation statements)

References 15 publications

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“…Because the progress of hypertension is normally followed by cardiac remodeling (Cohn et al, 2000; Duchatsch et al, 2020; Han et al, 2015; Hernandez et al, 2013; Pagan et al, 2015; Pagan et al, 2019; Rossoni et al, 2011), this present study evaluated the structural and functional changes determined by hypertension through the echocardiographic analysis and confirmed some previous results recently found by our group and others (Duchatsch et al, 2020; Han et al, 2015; J. Li et al, 2019) that SHR, even at 5 months, had higher LV relative wall thickness and increased LVMI, which can be induced by pressure overload (Bernardo et al, 2010). In fact, this increased LV RWT probably contributed to the reduced internal diameter during systolic and diastolic periods, as observed in these rats.…”

Section: Discussionmentioning

confidence: 99%

Differential effects of dexamethasone on arterial stiffness, myocardial remodeling and blood pressure between normotensive and spontaneously hypertensive rats

Tardelli

Duchatsch

Herrera

et al. 2021

J of Applied Toxicology

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Dexamethasone (DEX)‐induced hypertension is observed in normotensive rats, but little is known about the effects of DEX on spontaneously hypertensive animals (SHR). This study aimed to evaluate the effects of DEX on hemodynamics, cardiac hypertrophy and arterial stiffness in normotensive and hypertensive rats. Wistar rats and SHR were treated with DEX (50 μg/kg s.c., 14 d) or saline. Pulse wave velocity (PWV), echocardiographic parameters, blood pressure (BP), autonomic modulation and histological analyses of heart and thoracic aorta were performed. SHR had higher BP compared with Wistar, associated with autonomic unbalance to the heart. Echocardiographic changes in SHR (vs. Wistar) were suggestive of cardiac remodeling: higher relative wall thickness (RWT, +28%) and left ventricle mass index (LVMI, +26%) and lower left ventricle systolic diameter (LVSD, −19%) and LV diastolic diameter (LVDD, −10%), with slightly systolic dysfunction and preserved diastolic dysfunction. Also, SHR had lower myocardial capillary density and similar collagen deposition area. PWV was higher in SHR due to higher aortic collagen deposition. DEX‐treated Wistar rats presented higher BP (~23%) and autonomic unbalance. DEX did not change cardiac structure in Wistar, but PWV (+21%) and aortic collagen deposition area (+21%) were higher compared with control. On the other side, DEX did not change BP or autonomic balance to the heart in SHR, but reduced RWT and LV collagen deposition area (−12% vs. SHRCT). In conclusion, the results suggest a differential effect of dexamethasone on arterial stiffness, myocardial remodeling and blood pressure between normotensive and spontaneously hypertensive rats.

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Section: Discussionmentioning

confidence: 99%

Differential effects of dexamethasone on arterial stiffness, myocardial remodeling and blood pressure between normotensive and spontaneously hypertensive rats

Tardelli

Duchatsch

Herrera

et al. 2021

J of Applied Toxicology

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“…Both SHR groups had higher RT and -dT/dt than their respective controls. RT is mainly related to the myocardial collagen content ( Matsubara et al, 1997 ), which is increased in the senescent SHR ( Cezar et al, 2015 ; Pagan et al, 2015 , 2019 ). The –dT/dt values are dependent on the diastolic Ca 2+ removal from cytoplasm.…”

Section: Discussionmentioning

confidence: 99%

“…However, the effects of physical exercise during persistent pressure overload are not completely understood and both beneficial and adverse effects have been described ( Schultz et al, 2007 ; da Costa Rebelo et al, 2012 ; Locatelli et al, 2017 ; Schreckenberg et al, 2017 ). We have previously observed that low intensity aerobic exercise improves diastolic function by attenuating myocardial fibrosis and metalloproteinase-2 activity ( Pagan et al, 2015 , 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Aerobic Exercise During Advance Stage of Uncontrolled Arterial Hypertension

Pagan

Gomes

Damatto³

et al. 2021

Front. Physiol.

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AimTo evaluate the influence of physical training on myocardial function, oxidative stress, energy metabolism, and MAPKs and NF-κB signaling pathways in spontaneously hypertensive rats (SHR), at advanced stage of arterial hypertension, which precedes heart failure development.MethodsWe studied four experimental groups: normotensive Wistar rats (W, n = 27), trained W (W-EX, n = 31), SHR (n = 27), and exercised SHR (SHR-EX, n = 32). At 13 months old, the exercise groups underwent treadmill exercise 5 days a week for 4 months. In vitro myocardial function was analyzed in left ventricular (LV) papillary muscle preparations. Antioxidant enzyme activity and energy metabolism were assessed by spectrophotometry. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity was analyzed by lucigenin reduction and protein expression by Western blot. Statistical analyzes: ANOVA and Tukey or Kruskal–Wallis and Dunn tests.ResultsSHR-EX had a lower frequency of heart failure features than SHR. Myocardial function and antioxidant enzyme activity were better in SHR-EX than SHR. Lipid hydroperoxide concentration, and phosphorylated JNK and total IkB protein expression were higher in hypertensive than control groups. Malondialdehyde, NADPH oxidase activity, total JNK, phosphorylated p38, phosphorylated and total p65 NF-κB, and phosphorylated IkB did not differ between groups. Protein expression from total p38, and total and phosphorylated ERK were higher in SHR than W. Lactate dehydrogenase and phosphorylated ERK were lower and citrate synthase and β-hydroxyacyldehydrogenase were higher in SHR-EX than SHR.ConclusionExercise improves physical capacity, myocardial function, and antioxidant enzyme activity; reduces the frequency of heart failure features and ERK phosphorylation; and normalizes energy metabolism in SHR.

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“…We observed a large variety in overall study characteristics ( Supplementary Materials Table S1 ). The majority of studies used rodents: either mice (12 articles) [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ] or rats (6 articles) [ 49 , 50 , 51 , 52 , 53 , 54 ]. Other species included swine (n = 3) [ 55 , 56 , 57 ], rabbit (n = 1) [ 58 ] and guinea pig (n = 1) [ 59 ].…”

Section: Resultsmentioning

confidence: 99%

“…Given the pooled and separate effect of hemodynamic models on increased E/e’ ratio but lack of effect on E/A and E-wave, e’ seems to represent the most reliable change in LVDD/HFpEF. Indeed, Zhong et al [ 43 ], Pagan et al [ 51 ] and Sam et al [ 42 ] show a decreased e’ (3/5 comparisons). Clinically, e’ also has the highest reproducibility and a consistent association with CVD outcomes [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Extracellular Matrix Remodeling during Left Ventricular Diastolic Dysfunction and Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Analysis

Krebber

Dijk

Vernooij

et al. 2020

IJMS

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Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are pivotal regulators of extracellular matrix (ECM) composition and could, due to their dynamic activity, function as prognostic tools for fibrosis and cardiac function in left ventricular diastolic dysfunction (LVDD) and heart failure with preserved ejection fraction (HFpEF). We conducted a systematic review on experimental animal models of LVDD and HFpEF published in MEDLINE or Embase. Twenty-three studies were included with a total of 36 comparisons that reported established LVDD, quantification of cardiac fibrosis and cardiac MMP or TIMP expression or activity. LVDD/HFpEF models were divided based on underlying pathology: hemodynamic overload (17 comparisons), metabolic alteration (16 comparisons) or ageing (3 comparisons). Meta-analysis showed that echocardiographic parameters were not consistently altered in LVDD/HFpEF with invasive hemodynamic measurements better representing LVDD. Increased myocardial fibrotic area indicated comparable characteristics between hemodynamic and metabolic models. Regarding MMPs and TIMPs; MMP2 and MMP9 activity and protein and TIMP1 protein levels were mainly enhanced in hemodynamic models. In most cases only mRNA was assessed and there were no correlations between cardiac tissue and plasma levels. Female gender, a known risk factor for LVDD and HFpEF, was underrepresented. Novel studies should detail relevant model characteristics and focus on MMP and TIMP protein expression and activity to identify predictive circulating markers in cardiac ECM remodeling.

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Low‐intensity aerobic exercise improves cardiac remodelling of adult spontaneously hypertensive rats

Cited by 19 publications

References 15 publications

Differential effects of dexamethasone on arterial stiffness, myocardial remodeling and blood pressure between normotensive and spontaneously hypertensive rats

Differential effects of dexamethasone on arterial stiffness, myocardial remodeling and blood pressure between normotensive and spontaneously hypertensive rats

Aerobic Exercise During Advance Stage of Uncontrolled Arterial Hypertension

Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Extracellular Matrix Remodeling during Left Ventricular Diastolic Dysfunction and Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Analysis

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