Hydrogen Sulfide Inhibits Calcium-Induced Mitochondrial Permeability Transition Pore Opening in the Heart of Spontaneously Hypertensive Rats (original) (raw)

International Journal of Physiology and Pathophysiology, 2013

Abstract

ABSTRACT At in vivo and in vitro experiments on the mitochondria isolated from the heart tissue of control and spontaneously hypertensive rats (SHR), we examined the effects of NaHS, hydrogen sulfide donor, as well as L-cysteine, a substrate for its biosynthesis, on the sensitivity of mitochondrial permeability transition pore (mPTP) opening to the action of Ca2+, its natural inducer. The concentration dependence of the NaHS-evoked effect (10 6 – 10 4 mol / l) and calcium-induced heart mitochondrial swelling in both groups of animals has been revealed. The hydrogen sulfide donor in concentrations 10 6, 10 5 and 10 4 mol / l inhibited calcium-induced mPTP opening by 31, 76 and 100%, respectively, indicating that its protective effect on pore formation in the heart of control rats, with the normal blood pressure. Inhibition of mPTP in the heart of SHR requires an order of magnitude higher concentration of NaHS (10–5 – 10–4 mol / l) on the background of increased organelle capacity to pore formation. At in vivo experiments, a single intraperitoneal administration L-cysteine (10 3 mol / kg) resulted in reduced sensitivity to Ca2+, an mPTP inducer, in both groups. Inhibition of hydrogen sulphide biosynthesis in vivo by propargyl glycine (10–4 mol / kg), a specific inhibitor of cystathionine-γ-lyase, prevented the effect of L-cysteine in the heart of control rats, unlike SHR, where we observed a reduction of increased mPTP sensitivity to Ca2+. Thus, under physiological conditions and in hypertension, both exogenous and endogenous hydrogen sulfide have stabilizing effect on the mitochondrial membranes by increasing organelle resistance to Ca2+, a natural mPTP inducer. KEY WORDS: hydrogen sulfide, L-cysteine, mitochondrial permeability transition pore, heart, hypertension, rats

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