[Hydrogen sulfide inhibits Ca(2+)-induced mitochondrial permeability transition pore opening in spontaneously hypertensive rats].

Abstract

In experiments in vivo and in vitro on the mitochondria isolated from the control and spontaneously hypertensive rats (SHR) hearts, we studied the effects of a donor of hydrogen sulfide (H2S), NaHS, and H2S biosynthesis substrate, L-cysteine, on the sensitivity of the mitochondrial permeability transition pore (mPTP) opening to its natural inductor, Ca2+. We found that NaHS (10(-4), 10(-5) and 5 10(-5) mol/l) influenced the mitochondrial swelling in a concentration-dependent manner in control and spontaneously hypertensive rats. The H2S donor NaHS used in physiological concentrations (10(-6), 10(-5) and 5 10(-5) mol/l) exerted the inhibiting effect on the Ca(2+)-induced mPTP opening in control hearts (corresponding values of such effect were 31, 76, and 100%, respectively), while in spontaneously hypertensive rats hearts the protector effect of NaHS was observed only at its concentration of 10(-5) - 10(-4) mol/l. In experiments in vivo, single intraperitoneal injections of L-cysteine (10(-3) mol/kg) resulted in a decrease in the sensitivity of mPTP to it's inductor Ca2+ in control rats and SHR. In experiments in vivo in which we used a specific blocker of cystathionine-gamma-lyase, propargylglycine (10(-4) mol/kg), with the further injections of L-cysteine we observed a decrease in the threshold Ca2+ concentration (that induce the mitochondrial swelling) by three orders of magnitude in SHR, but in control rats did not effect of L-cysteine. Thus, both endogenous and exogenous hydrogen sulfide inhibits Ca(2+)-induced mitochondrial permeability transition pore opening, indicating its protective effect on pore formation in spontaneously hypertensive rats hearts. Therefore, our studies are indicative of the involvement of H2S in modulation of changes in the permeability of mitochondrial membranes, which can be an important regulatory factor in the development of cardiovascular diseases.