On anaesthetised dogs the role NO and mitochondrial permeability transition pore (MPTP) in the regulation of regional blood circulation, efficiency of oxygen using, and muscle contraction force was investigated. Injection NOS inhibitor L-NMMA resulted in pronounced fall of a functional hyperaemia magnitude, significant reduction of the muscle contractions force and efficiency of oxygen using in m.gastrocnemicus, in comparison with control. Pretreatment with an activator of MPTP phenilarsineoxide (PAO) was caused the marked inhibition of an endothelium-dependent reaction of functional hyperaemia on skin-muscle region of rear limb. At the same time the muscle contractions force was significance decreased and efficiency of oxygen using was diminished too. That was accompanied by an appearance in blood from v. femoralis mitochondrial factor (MF), it was evidence of MPTP activation. The preliminary injection of the NO donor - sodium nitroprusside prevented considerably an inhibition of a dilation vessel's reserve, a fall of muscle contractions force and considerably reduced oxygen cost of a m.gastercnemicus work also. The concentration of MF in blood from v. femoralis also was considerably reduced that has been evidence of MPTP inhibition. Thus, NO in physiological concentration, inhibitioning the mPTP opening, can prevent decrease of efficiency of oxygen using and development of the working skeletal muscle fatigue.