P498Hydrogene sulfide as mediator of adaptation to physical training.

Hydrogen sulfide is enzymaticaly synthesized by three enzymes - cystathionine gama-lyase (CSE), cystathionine beta-lyase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST). After physical training of rats (4 weeks swimming course) we observed in myocardium the increased of these enzymes expression (in 1,5; 2,5 and 5 times accordingly), which accompanied with increased H2S content in myocardium (31,65±1.29 vs 12,6±0,31 nmol/mg protein in control), in miocardial mitochondria (10,55±1,2 vs 4,2±1,1 nmol/mg protein in control) and in plasma (3,75±0,22 vs 2,48±0,08 nmol/mg protein in control). However, it reminds unclear how H2S takes part in myocardial adaptation to workload, which accompanied with increased heart inflow and intracellular calcium content. Using isolated rat heart by Langendorff preparation we studied myocardial response to gradually increased left ventricular volume (Frank-Starling low) and increasing concentration of Ca2+ in perfusion solution (from 1.7mM to 12.5 mM) in trained and untrained rats. It was shown that swimming course improved heart function: heart rate was decreased, contractile activity (dP/dt max, developing isovolumic LV pressure) and coronary flow were increased by 20% and 33% respectively. Equal volume stretching of balloon in left ventricle provoked greater contraction in trained comparing to untrained hearts, demonstrating extended functional reserves after swimming course. Furthermore, training significantly increased mitochondrial membrane potential in isolated mitochondria (-176,5±8,4 mV vs -156±3,5 mV in control), that points to improved efficiency of oxidative phosphorylation. The mitochondrial permeability transition pore (MPTP) in trained heart was detected at higher concentration of calcium that reveals extended calcium capacity of mitochondria and lesser sensitivity of MPTP to its inductor - calcium. In experiments on isolated mitochondria was shown that blockade of H2S synthesis increased but its high level decreased of MPTP sensitivity to calcium. High level of myocardial H2S increased Frank-Starling reaction too.Thus, heart adaptation to physical training and extend of functional reserves of heart are provided by endogenous H2S production and its effects on MPTP sensitivity to calcium.