Involvment of nitric oxide and MPTP in heart adaptation to physical training

Abstract

After physical training of rats (4 weeks swimming) we observed in myocardium and aorta the activation of both salvage and de novo nitric oxide synthesis, an increase in nitric oxide bioavailability and endothelium-dependent vasorelaxation. However, it reminds unclear how NO takes part in myocardial adaptation to workload. Using isolated rat heart by Langendorf preparation we studied myocardial response to gradually increased left ventricular volume (Frank-Starling low) and increasing concentration of Ca2+ in perfusion solution (from 1.7 mM to 12,5 mM) in trained and untrained rats. It was shown that swimming improved heart function: heart rate was decreased, contractile activity 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, trainingsignificantly increased mitochondrial membrane potential in isolatedmitochondria (−176.5 ± 8.4 mV vs −56 ± 3.5 mV in control), that points to improved efficiency of oxidative phosphorylation. The opening of 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. Blockade of NO synthesis with L-NAME application of (10–4 M for 15 min) abolished reaction of trained heart during Frank-Starling and calcium upload. NOS inhibition prevented the increased functional hyperaemia of the hearts from trained rats. Thus, heart adaptation to physical training and extend of functional reserves of heart are provided by increased endogenous NO production.