The Molecular Mechanism Of20-HETE Released By Exercise-induced Fatigue Cause Myocardial Damage

20-hydroxyeicosatetraenoic acid (20-HETE) is a metabolite of arachidonic acid catalyzed by the omega-hydroxylase of the cytochrome P-450, which is an important vasoconstrictor. However, whether exercise-induced fatigue can induce the release of endogenous substance20～HETE, and lead to the change of calcium transient, Myocardial mechanics and L-type calcium current have not been reported. The rats were randomly divided into3groups, including the control group, the exercise fatigue group, the exercise fatigue+HET0016(20-HETE inhibitors) group. The rat exercise-induced fatigue models were established by swimming for15days.1) by using Langendorff exzamines the heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and maximal rise and decline rate of ventricular pressure (+dp/dtmax),2)using rat isolated cardiomyocytes by patch-clamp in the whole cell mode records L-type Ca2+current.3)Isolated cardiomyocyte cells incubated with Fluo-3fluorescent dye,then uses Laser confocal microscope to record calcium transients. Main results are as following:We discover that compared with the control group, the exercise fatigue group HR increase22.4%(from250±11beats/min to306±18beats/min), myocardial mechanics index LVSP decrease34.03%(from85.8±11.0to56.6±12.4),+dp/dtmax. decrease21.38%(from896.4±18.1to704.7±17.8);-dp/dtmax decrease23.28%(from660.2±15.3to506.5±31.6) LVEDP, LVEDP increase53.11%(from20.9±1.1to32.0±1.9),the change of these indexes suggest that exercise fatigue injured the myocardium; Meanwhile, we find that L-type Ca2+current increase85.17%and11.11%increase in the amplitude of calcium transients. After the injection of20-HETE inhibiter HET0016, these indicators basically recovered to the control level, demonstates that HET0016effectively inhibites the change caused by exercise fatigue, and exercise fatigue lead to the release of20-HETE.All the results above showed that the exercise fatigue leads to the release of endogenous substance20-HETE, resulting in the change of myocardial mechanics and calcium, and exercise fatigue cause the change of myocardial mechanics via20-HETE activating L-type calcium channel, result in increased calcium influx, lead to intracellular calcium overload, cause myocardial mechanics change;...