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EXCLI J. 2015 Oct 14;14:1104-15. doi: 10.17179/excli2015-510. eCollection 2015.

Synergistic effects of nitric oxide and exercise on revascularisation in the infarcted ventricle in a murine model of myocardial infarction.

EXCLI journal

Kamal Ranjbar, Farzad Nazem, Afshin Nazari, Mohammadreza Gholami, Ali Reza Nezami, Malihe Ardakanizade, Maryam Sohrabi, Hasan Ahmadvand, Mohammad Mottaghi, Yaser Azizi

Affiliations

  1. Department of Sport Physiology, Faculty of Physical Education and Sport Sciences, Bu-Ali Sina University, Hamedan, Iran.
  2. Department of Physiology, Razi Herbal Medicine Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran.
  3. Department of Anatomy, Lorestan University of Medical Sciences, Khorramabad, Iran.
  4. Department of cardiology, Shahid madani hospital, Lorestan University of Medical Sciences, Khorramabad, Iran.
  5. Department of Anatomy, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
  6. Department of Biochemistry, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran.
  7. Department of Physiology, Physiology research center, School of Medicine, Iran Universty of Medical Sciences, Tehran, Iran.

PMID: 26869868 PMCID: PMC4746998 DOI: 10.17179/excli2015-510

Abstract

It has been shown that density of microvessels decreases in the left ventricular after myocardial infarction (MI). The change of angiogenic and angiostatic factors as the main factors in revascularisation after exercise training in area at risk is not determined yet in MI. Therefore, the aim of the present study was the effect of exercise training and L-arginine supplementation on area at risk angiogenesis in myocardial infarction rat. Four weeks after surgery (Left Anterior Descending Coronary artery Ligation), myocardial infarction rats were divided into 4 groups: Sedentary rats (Sed-MI); L-arginine supplementation (La-MI); Exercise training (Ex-MI) and Exercise + L-arginine (Ex+La). Exercise training (ET) lasted for 10 weeks at 17 m/min for 10-50 min day(-1). Rats in the L-arginine-treated groups drank water containing 4 % L-arginine. After ET and L-arginine supplementation, ventricular function was evaluated and angiogenic and angiostatic indices were measured at ~1 mm from the edge of scar tissue (area at risk). Statistical analysis revealed that gene expression of VEGF as an angiogenic factor, angiostatin as an angiostatic factor and caspase-3 at area at risk decrease significantly in response to exercise training compared to the sedentary group. The capillary and arteriolar density in the Ex groups were significantly higher than those of the Sed groups. Compared to the Ex-MI group, the Ex+La group showed a markedly increase in capillary to fiber ratio. No significant differences were found in infarct size among the four groups, but cardiac function increased in response to exercise. Exercise training increases revascularization at area at risk by reduction of angiostatin. L-arginine supplementation causes additional effects on exercise-induced angiogenesis by preventing more reduction of VEGF gene expression in response to exercise. These improvements, in turn, increase left ventricular systolic function and decrease mortality in myocardial infarction rats.

Keywords: L-arginine; angiogenesis; cardiac function; exercise training; myocardial infarction

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