Testosterone confers cardioprotective effect on rat heart via mitochondrial ATP‐senstitive potassium channel

Abstract

In this study, we examined whether testosterone might improve myocardial tolerance to ischemia via activating mitochondrial KATP channels (mitoKATP) and depressing mitochondrial permeability transition pore (mitoPTP). Sprague-Dawley rats were approximately eight weeks old at the time of surgery. For the gonadectomized group, the vas deferens were ligated bilaterally and the testes removed. The replacement of testosterone propionate (200 g/mg/d) began 1 week after gonadectomy. Eight weeks later, in isolated hearts subjected to regional ischemia, testosterone treatment improved the recovery of rate-pressure product and coronary flow during reperfusion, and reduced the infarct size and release of lactate dehydrogenase. Administration of 20 μmol/L atractyloside, a mitoPTP opener, for the last 5 min of ischemia and first 15 min of reperfusion, or pretreatment with 100 μmol/L 5-HD, an inhibitor of the mitoKATP channel, for 10 min before ischemia, attenuated the beneficial effect by testosterone. In cultured cardiomyocytes pretreated with 10 μmol/L testosterone for 20 min, a significant inhibition of H2O2-induced cell death was observed, while 5- HD attenuated the inhibition. These findings indicate that testosterone protects the myocardium against ischemia and reperfusion injury by inhibiting mitochondrial permeability transition pore opening as well as activating mitoKATP channels.