Abstract
Introduction
Physical exercise reduces systemic arterial blood pressure and improves cardiac remodeling. However, the effects of exercise during uncontrolled arterial hypertension remains poorly understood. This study evaluated the influence of physical training on cardiac remodeling in untreated spontaneously hypertensive rats (SHR).
Methods
Four experimental groups were used: sedentary (W-SED n=27) and trained (W-EX, n=31) normotensive Wistar rats, and sedentary (SHR-SED, n=27) and exercised (SHR-EX, n=32) hypertensive rats. At 13 months old, the exercise groups underwent treadmill exercise five days a week, for four months. Echocardiogram was performed to evaluate cardiac structures and function. In vitro myocardial function was analyzed in left ventricular (LV) papillary muscle preparations. Myocardial collagen was quantified by histology and hydroxyproline concentration and antioxidant enzyme activity was assessed by spectrophotometry. NADPH oxidase activity was analyzed by lucigenin reduction. Protein expression was quantified by Western blot. Matrix metalloproteinases (MMP) activity was evaluated by zymography. Statistical analyzes: two factor ANOVA and Bonferroni or Kruskal-Wallis and Dunn tests.
Results
Systolic blood pressure was higher in SHR groups. Exercised groups had greater physical capacity. Frequency of heart failure features was higher in hypertensive groups than controls; SHR-EX had a lower frequency of pleural effusion and tachypnea than SHR-SED. Echocardiogram showed lower LV wall thickness, LV relative wall thickness, left atrium diameter, and relaxation time in SHR-EX than SHR-SED. Myocardial function was better in SHR-EX (positive derivative of developed tension) than SHR-SED. SHR-EX had higher antioxidant enzyme activity than SHR-SED. Lipid hydroperoxide concentration, myocyte diameters, and phosphorylated JNK and total IkB protein expression were higher in hypertensive than control groups. Hydroxyproline, malondialdehyde, NADPH oxidase activity, and protein expression of collagen III, lysyl oxidase, TIMP-1, total JNK, phosphorylated p38, phosphorylated and total p65, and phosphorylated IkB did not differ between groups. Interstitial collagen fraction, MMP-2 activity, and protein expression of total p38, and total and phosphorylated ERK were higher in SHR-SED than W-SED. Exercise reduced MMP-2 activity and phosphorylated ERK in hypertensive rats.
Conclusion
Physical exercise improves physical capacity, reduces the frequency of heart failure features, and attenuates cardiac remodeling in spontaneously hypertensive rats. In addition, exercise increases antioxidant enzyme activity, decreases ERK phosphorylation and MMP-2 activity, and attenuates total ERK protein expression.
Acknowledgement/Funding
Fapesp, CNPq, Capes and UNESP
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