Exercise enhances myocardial ischemic tolerance via an opioid receptor-dependent mechanism

Abstract

Exercise increases serum opioid levels and improves cardiovascular health. Here we tested the hypothesis that opioids contribute to the acute cardioprotective effects of exercise using a rat model of exercise-induced cardioprotection. For the standard protocol, rats were randomized to 4 days of treadmill training and 1 day of vigorous exercise (day 5), or to a sham exercise control group. On day 6, animals were killed, and global myocardial ischemic tolerance was assessed on a modified Langendorff apparatus. Twenty minutes of ischemia followed by 3 h of reperfusion resulted in a mean infarct size of 42 +/- 4% in hearts from sham exercise controls and 21 +/- 3% (P < 0.001) in the exercised group. The cardioprotective effects of exercise were gone by 5 days after the final exercise period. To determine the role of opioid receptors in exercise-induced cardioprotection, rats were exercised according to the standard protocol; however, just before exercise on days 4 and 5, rats were injected subcutaneously with 10 mg/kg of the opioid receptor antagonist naltrexone. Similar injections were performed in the sham exercise control group. Naltrexone had no significant effect on baseline myocardial ischemic tolerance in controls (infarct size 43 +/- 4%). In contrast, naltrexone treatment completely blocked the cardioprotective effect of exercise (infarct size 40 +/- 5%). Exercise was also associated with an early increase in myocardial mRNA levels for several opioid system genes and with sustained changes in a number of genes that regulate inflammation and apoptosis. These findings demonstrate that the acute cardioprotective effects of exercise are mediated, at least in part, through opioid receptor-dependent mechanisms that may include changes in gene expression.

Hemodynamic effects of atrial natriuretic peptide in ischemia-reperfusioninjury that occurs after exercise

“…A standard exercise protocol was applied in the exercised rats similar to another study (11). Exercise groups were exposed to a running protocol for 5 days according to this protocol.…”

“…This period was accepted as moderate exercise and also as a training period to prepare the animals for the last day of vigorous exercise. The vigorous exercise of the 5th day lasted 25 min at 25 m/min (11). At the end of the vigorous exercise period, the animals were killed, their hearts were harvested, and isolated hearts were perfused within 1 h after the last bout of exercise.…”

Atriyal natriüretik peptid infüzyonunun izole sıçan kalbinde iskemi sonrası oluşturduğu hemodinamik değişikliklerde egzersizin rolü

“…Kısa süreli egzersizlerin kalpteki iskemi-reperfüzyon hasarı açısından pozitif yönde değişiklikler oluş-turduğu, miyokardiyal tolerans ve kan akımıyla uyarılan vazodilatasyonda artış meydana getirdiği bildirilmektedir (11,13,14). Sıçanlar üzerinde uygulanan kısa süreli egzersizler genelde 1-10 günlük bir zaman periyodunda yaptı-rılan egzersizlerdir.…”

“…Bu çalışmada egzersiz grubunda yer alan sıçanlarda daha önceki bir çalışmaya benzer bir egzersiz programı uygulandı (11). E ve E-ANP gruplarında yer alan sıçanlara koşu bandında 5 günlük bir egzersiz programı uygulandı.…”

Effects of anaerobic exercise and detraining on the caspase-3 expression of rat ventricular cardiomyocyte

“…Risk of sudden cardiac death was also 2.5 times higher in athletes than those who do not exercise. 9,10 High intensity physical exercise causes an increase in myocardial oxygen demand and requires more oxygen supply, which can induce cardiac hypertrophy both physiological and pathological. 11 Animal study in rat showed that physical exercise for four days, 10 days, and 13 weeks are associated with chronic excessive pressure load on the heart that stimulates apoptosis.…”