Activation of Endogenous Hydrogen Sulfide Synthesis Inhibits Mitochondrial Permeability Transition Pore Opening and Restores Constitutive NO-Synthase Coupling in Old Rat Heart

We studied effects of pyridoxal-5-phosphate (P5P), as a cofactor for H2S synthesizing enzyme, on the sensitivity of mitochondrial permeability transition pore (MPTP) opening to Ca,2+ its natural inducer, in old rat heart, as well as H2S content, oxidative and nitrosative stress indicators in the heart mitochondria. It has been shown that in old rats oxidative and nitrosative stress develop, which is accompanied by a decrease in the constitutive Ca2+ -dependent NO-synthase (cNOS) coupling index. P5P application inhibits Ca2+ -induced MPTP opening by reducing the sensitivity to the inductor in old rat heart. Applying a modulator of H2S synthesis results in an increase in hydrogen sulfide content 4.2 times and promotes a decrease in O2- generation speed 3.5 times in comparison with these indicators in old animals. An important consequence of stimulating hydrogen sulfide endogenous synthesis in aging is the increase in cNOS activity 1.9 times and a decrease in the activity of Ca2+ -independent inducible NO-synthase (iNOS) 4.3 times in the heart mitochondria. Under these conditions, cNOS coupling index in organelles increases 8.7 times, relative to the values in old animals. Thus, H2S acts as a regulator of MPTP opening and NO content, by increasing cNOS activity and restituting the enzyme coupled state, which indicates the role of this gaseous transmitter in cardiovascular pathology.