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

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.

[Cardiohemodynamics and efficiency Frank-Starling mechanism in spontaneously hypertensive rats].

We studied cardiohemodynamics and efficiency Frank-Starling mechanism in 6-month-old spontaneously hypertensive rats (SHR) and age-matched Wistar rats, using pressure-volume (PV) conductance catheter system (Millar Instruments, Houston, TX) to evaluate systolic and diastolic function in vivo. Rats were anesthetized with urethane. Cardiohemodynamics analyzed using PVAN 3.6 (Millar Instruments). We found that systolic and diastolic function of the heart in spontaneously hypertensive rats were lower, than in controls. We have shown, inhibition of the efficiency Frank-Starling mechanism, increasing arterial stiffness in spontaneously hypertensive rats. It's shown, less efficiency heart work, with more energy and more oxygen consumption in spontaneously hypertensive rats, may be associated with increasing arterial stiffness and decrease functional reserve of the heart.

[Increase in the sensitivity of the mitochondrial permeability transition pore opening to Ca2+ in heart of spontaneous hypertensive rat].

In experiments vitro on the mitochondria isolated from adult and spontaneous hypertensive rat hearts, we studied the sensitivity of the mitochondrial permeability transition pore (mPTP) opening to its natural inductor, Ca2+. We observed an increase in the sensitivity of mPTP opening to Ca2+ in the heart of spontaneous hypertensive rats because of a decrease in the threshold concentration of this ion required for organelles swelling by two orders of magnitude. It was shown that the classical inhibitor mPTP cyclosporin A (10(-5) mol/L) partially (54%) inhibited of mPTP opening in the heart of these animals, indicating that the presence in the heart of these animals of cyclosporin A-insensitive component of the mPTP. The results of our observations give reason to conclude that the hypertensive state of the organism is associated with mitochondrial dysfunction, which is characterized, in particular, by an increased sensitivity mPTP to Ca2+, eliciting a widespread tissue damage and diseases of the cardiovascular system, especially hypertension.

[The mitochondrial membrane potential and oxygen consumption in the heart of spontaneously hypertensive rats].

We investigated the mitochondrial membrane potential and processes of respiration and oxidative phosphorylation in suspension of cardiac mitochondria from 6 month old spontaneously hypertensive rats (SHR) and Wistar (as a control) male rats. The mitochondrial membrane potential and the speed of oxygen consumption were measured using the method described by M.Brand (1995). Processes of respiration and oxidative phosphorylation in cardiac mitochondria were measured using Oxygraph (Hansatech instruments, Norfolk, England). It has been found that in SHR the mitochondrial membrane potential was lower (-113.76 mV+/-3.65 mV) compared to Wistar rats (DeltaPsim=-152.85 mV+/-13.52 mV, p<0.01). In SHR, the respiration rate in state V2 by Chance and V3 were increased compared to Wistar rats (p<0.001). The respiration control by Chance was depressed by 23.9% in SHR compared to Wistar rats. Our data demonstrate, that SHR have some features of functioning of cardiac mitochondria which distinguish them from the Wistar rats. Our data suggest a functional link between mitochondrial energy supply and arterial hypertension.