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International Journal of Physiology and Pathophysiology

Publicou 4 edições por ano

ISSN Imprimir: 2155-014X

ISSN On-line: 2155-0158

SJR: 0.116

Inhibition of Mitochondrial Hydrogen Sulfide Production Worsens Heart Contractility and Enhances Sensitivity of Mitochondrial Permeability Transition Pore to Calcium

Volume 9, Edição 2, 2018, pp. 135-142
DOI: 10.1615/IntJPhysPathophys.v9.i2.50
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RESUMO

We examined the involvement of hydrogen sulfide (H2S) catalyzed by mitochondrial enzyme 3-mercaptopyruvate-sulfurtransferase (3-MST) in cardiac tolerance to calcium load and regulation of mitochondrial permeability transition pore (MPTP) opening. In isolated rat heart, it has been revealed that the enzyme inhibition by O-carboxymethyl hydroxylamine (O-CMH) (50 mg/kg, i.p., 30 min before the experiment start) results in worsening of all heart indices. In particular, the left ventricular developing pressure (LVDP), as well as myocardium contraction/relaxation rate (dP/dt) decreased by 50%. When modeling calcium load, CMH induced a rapid increase in LV end-diastolic pressure and developing of arhythmias. Further modeling of Ca2+ loads was accompanied by lower increment of LVDP and dP/dt comparing to that in control rats indicating low functional reserves and low Ca2+ efficacy in O-CMH-pretreated rats. Cardiac mitochondria in O-CMH group were more sensitive to Ca2+ showing maximum swelling at 10−5 moles/L in the incubation medium vs 10−4 moles/L in control group (p < 0.05). Preincubation of cardiac mitochondria with O-CMH in concentrations of 10−5, 10−4, and 10−3 moles/L evoked an increase in Ca2+ -induced swelling by 17.8, 20, and 44%, respectively. An inhibition of mitochondrial pathway of H2S synthesis increased heart mitochondria sensitivity to Ca2+, which resulted in swelling of mitochondrial membranes and low ability of myocardium to manage Ca2+ homeostasis under Ca2+ loads. Thus, it has been found that endogenous hydrogen sulfide of mitochondrial origin is involved in the regulation of MPTP opening, and also plays an important role in regulating the heart functioning.

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