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We evaluated the influence of aerobic training on cardiac remodeling in untreated spontaneously hypertensive rats (SHR). Four experimental groups were used: sedentary (W-SED, n=27) and trained (WEX, n=31) normotensive Wistar rats, and sedentary (SHR-SED, n=27) and exercised (SHR-EX, n=32) hypertensive rats. At 13 months old, trained groups underwent treadmill exercise five days a week for four months. Statistical analysis: ANOVA or Kruskal-Wallis. Exercised groups had higher physical capacity. Hypertensive groups presented left ventricular (LV) concentric hypertrophy with impaired function. Left atrium diameter, LV posterior wall thickness and relative thickness, and isovolumetric relaxation time were lower in SHR-EX than SHR-SED. Interstitial collagen fraction and Type I-Type III collagen ratio were higher in SHR-SED than W-SED. In SHR-EX these parameters had intermediate values between W-EX and SHRSED with no differences between either group. Myocardial matrix metalloproteinase-2 activity, evaluated by zymography, was higher in SHR-SED than W-SED and SHR-EX. TIMP-2 was higher in hypertensive than normotensive groups. In conclusion, low intensity aerobic exercise reduces left atrium dimension and LV posterior wall thickness, and improves functional capacity, diastolic function, and metalloproteinase-2 activity in adult SHR., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Background: Information on the role of intermittent fasting (IF) on pathologic cardiac remodeling is scarce. We compared the effects of IF before and after myocardial infarction (MI) on rat cardiac remodeling and survival., Methods: Wistar rats were intermittently fasted (food available every other day) or fed ad libitum for 12 weeks and then divided into three groups: AL - fed ad libitum; AL/IF - fed AL before MI and IF after MI; and IF - fed IF before and after MI. Echocardiogram was performed before MI and 2 and 12 weeks after surgery. Isolated hearts were evaluated in Langendorff preparations., Results: Before surgery, body weight (BW) was lower in IF than AL. Final BW was lower in AL/IF and IF than AL. Perioperative mortality did not change between AL (31.3%) and IF (27.3%). Total mortality was lower in IF than AL. Before surgery, echocardiographic parameters did not differ between groups. Two weeks after surgery, MI size did not differ between groups. Twelve weeks after MI, left ventricular (LV) diastolic posterior wall thickness was lower in AL/IF and IF than AL. The percentage of variation of echocardiographic parameters between twelve and two weeks showed that MI size decreased in all groups and the reduction was higher in IF than AL/IF. In Langendorff preparations, LV volume at zero end-diastolic pressure (V0; AL: 0.41 ± 0.05; AL/IF: 0.34 ± 0.06; IF: 0.28 ± 0.05 mL) and at 25 mmHg end-diastolic pressure (V25; AL: 0.61 ± 0.05; AL/IF: 0.54 ± 0.07; IF: 0.44 ± 0.06 mL) was lower in AL/IF and IF than AL and V25 was lower in IF than AL/IF. V0/BW ratio was lower in IF than AL and LV weight/V0 ratio was higher in IF than AL. Myocyte diameter was lower in AL/IF and IF than AL (AL: 17.3 ± 1.70; AL/IF: 15.1 ± 2.21; IF: 13.4 ± 1.49 μm). Myocardial hydroxyproline concentration and gene expression of ANP, Serca 2a, and α- and β-myosin heavy chain did not differ between groups., Conclusion: Intermittent fasting initiated before or after MI reduces myocyte hypertrophy and LV dilation. Myocardial fibrosis and fetal gene expression are not modulated by feeding regimens. Benefit is more evident when intermittent fasting is initiated before rather than after MI.

Background: Increased reactive oxygen species (ROS) generation in diabetes mellitus (DM) is an important mechanism leading to diabetic cardiomyopathy. Apocynin, a drug isolated from the herb Picrorhiza kurroa, is considered an antioxidant agent by inhibiting NADPH oxidase activity and improving ROS scavenging. This study analyzed the influence of apocynin on cardiac remodeling in diabetic rats., Methods: Six-month-old male Wistar rats were assigned into 4 groups: control (CTL, n = 15), control + apocynin (CTL + APO, n = 20), diabetes (DM, n = 20), and diabetes + apocynin (DM + APO, n = 20). DM was induced by streptozotocin. Seven days later, apocynin (16 mg/kg/day) or vehicle was initiated and maintained for 8 weeks. Left ventricular (LV) histological sections were used to analyze interstitial collagen fraction. NADPH oxidase activity was evaluated in LV samples. Comparisons between groups were performed by ANOVA for a 2 × 2 factorial design followed by the Bonferroni post hoc test., Results: Body weight (BW) was lower and glycemia higher in diabetic animals. Echocardiogram showed increased left atrial diameter, LV diastolic diameter, and LV mass indexed by BW in both diabetic groups; apocynin did not affect these indices. LV systolic function was impaired in DM groups and unchanged by apocynin. Isovolumic relaxation time was increased in DM groups; transmitral E/A ratio was higher in DM + APO compared to DM. Myocardial functional evaluation through papillary muscle preparations showed impaired contractile and relaxation function in both DM groups at baseline conditions. After positive inotropic stimulation, developed tension (DT) was lower in DM than CTL. In DM + APO, DT had values between those in DM and CTL + APO and did not significantly differ from either group. Myocardial interstitial collagen fraction was higher in DM than CTL and did not differ between DM + APO and CTL + APO. Serum activity of antioxidant enzymes glutathione peroxidase, superoxide dismutase (SOD), and catalase was lower in DM than CTL; apocynin restored catalase and SOD levels in DM + APO. Myocardial NADPH oxidase activity did not differ between groups., Conclusion: Apocynin restores serum antioxidant enzyme activity despite unchanged myocardial NADPH oxidase activity in diabetic rats.

Unlabelled: Aldosterone plays a pivotal role in the pathophysiology of systolic heart failure. However, whether early aldosterone antagonism improves cardiac remodeling during persistent pressure overload is unsettled. We evaluated the effects of aldosterone antagonist spironolactone on cardiac remodeling in rats with ascending aortic stenosis (AS)., Methods: Three days after inducing AS, weaning rats were randomized to receive spironolactone (AS-SPR, 20mg/kg/day) or no drug (AS) for 18weeks, and compared with sham-operated rats. Myocardial function was studied in isolated left ventricular (LV) papillary muscles., Statistical Analyses: ANOVA or Kruskal-Wallis tests., Results: Echocardiogram showed that LV diastolic (Sham 8.73±0.57; AS 8.30±1.10; AS-SPR 9.19±1.15mm) and systolic (Sham 4.57±0.67; AS 3.61±1.49; AS-SPR 4.62±1.48mm) diameters, left atrial diameter (Sham 5.80±0.44; AS 7.15±1.22; AS-SPR 8.02±1.17mm), and LV mass were higher in AS-SPR than AS. Posterior wall shortening velocity (Sham 38.5±3.8; AS 35.6±5.6; AS-SPR 31.1±3.8mm/s) was lower in AS-SPR than Sham and AS; E/A ratio was higher in AS-SPR than Sham. Developed tension was lower in AS and AS-SPR than Sham. Time to peak tension was higher in AS-SPR than Sham and AS after post-rest contraction. Right ventricle weight was higher in AS-SPR than AS, suggesting more severe heart failure in AS-SPR than AS. Interstitial collagen fractional area and myocardial hydroxyproline concentration were higher in AS than Sham. Metalloproteinase-2 and -9 activity, evaluated by zymography, did not differ between groups., Conclusion: Early spironolactone administration causes further hypertrophy in cardiac chambers, and left ventricular dilation and dysfunction in rats with AS-induced chronic pressure overload., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)