Role of calcium and potassium channels in effects of hydrogen sulfide on frog myocardial contractility

The effects of sodium hydrosulfide NaHS, a donor of hydrogen sulfide H 2S, on the force of muscle contraction were examined on isolated myocardial strips from frog ventricles. NaHS decreased the amplitude of muscle contractions in a dose-dependent manner under normal conditions and during inhibition of Ca channels with nifedipine. In contrast, under conditions of blockade of ATP-dependent potassium channels with glibenclamide, NaHS exerted a positive inotropic effect from the first minute of application. Neither blockade, nor activation of ATP-dependent K-channels with glibenclamide modulated the negative inotropic effect of NaHS. Inhibition of K-channels with tetraethylammonium (TEA) (3, 5, 10 mM) or 4-aminopyridine increased the amplitude of myocardial contractions. Preliminary application of 4-aminopyridine or TEA (3 mM) did not eliminate NaHS-induced negative inotropic effect, although higher TEA concentrations (5 or 10 mM) prevented it. The data indicate that the targets of H2S in frog myocardium are ATP-dependent, Ca-activated, and voltage-dependent K-channels. © 2011 Springer Science+Business Media, Inc

Hydrogen sulfide in regulation of frog myocardium contractility

Hydrogen sulfide (H2S) is an endogenously synthesized gaseous molecule which along with nitric oxide and carbon monoxide induces a number of effects in cardiovascular system in normal and pathological conditions. In the present study the effects and underlying mechanisms of H2S donor, sodium hydrosulfide (NaHS), on isometric force of frog myocardium contraction were studied. NaHS in the concentration of 100 μM induced a negative inotropic effect and decreased the maximal velocity of contraction and relaxation of isolated ventricle strips. The substrate Of H2S synthesis L-cystein (200 μM and 1 mM) induced the same effect and the inhibitors of cystationin y-lyase, H2S-producing enzyme in heart, ß-cyanoalanin (500 μM) and propargylglycine (500 μM) increased the amplitude of contraction. Inhibition of cystationin y-lyase by ß-cyanoalanin prevented the negative inotropic effect of L-cystein. After inhibition of adenylate cyclase by MDL12,330A (3 μM) or phosphodiesterases by IBMX (200 μM) effect of NaHS was lesser than in control. In the presence of membrane-penetrating analogous of cAMP, 8Br-cAMP (100 μM) and pCPT-cAMP (100 μM), negative inotropic effect of NaHS completely retained. The effect of NaHS significantly decreased after preliminary application of the NO donor, SNAP (10 μM), and did not change after inhibition of NO-synthases by LNAME ( 100 μM). The obtained data suggest the possibility of endogenous synthesis of H2S in frog myocardium and regulation of its contractility by activation of phosphodiesterases hydrolyzing cAMP, which leads to a decrease of activation of cAM P-dependent protein kinases and phosphorylation of voltage-dependent L-type Ca-channels. As the result, a reduction of calcium entry into cardiomyocytes decreases the contractility of frog myocardium

Hydrogen sulfide in regulation of frog myocardium contractility

Hydrogen sulfide (H2S) is an endogenously synthesized gaseous molecule which, along with nitric oxide and carbon monoxide, induces a number of effects in cardiovascular system under normal and pathological conditions. In the present work, the effects and underlying mechanisms of the H2S donor sodium hydrosulfide (NaHS) on the isometric force of frog myocardium contraction have been studied. NaHS at the concentration of 100 μM induced negative inotropic effect and reduced the maximum velocity of the contraction and relaxation of the isolated ventricle strips. The substrate of H2S synthesis, L-cysteine (200 μM and 1 mM), induced the same effect, while the inhibitors of cystathionin-γ-lyase, the H2S-producing enzyme in heart, β-cyanoalanine (500 μM) and propargylglycine (500 μM), increased the amplitude of contraction. Inhibition of cystathionin-γ-lyase by β-cyanoalanine prevented the negative inotropic effect of L-cysteine. After the inhibition of adenylate cyclase by MDL-12,330A (3 μM) or phosphodiesterases by IBMX (200 μM), the effect of NaHS was less than that in the control. In the presence of membrane-penetrating analogous of cAMP, 8Br-cAMP (100 μM) and pCPT-cAMP (100 μM), the negative inotropic effect of NaHS was completely retained. The effect of NaHS significantly decreased after preliminary application of the NO donor, SNAP (10 μM), and did not change after the inhibition of NO synthases by L-NAME (100 μM). The results suggest the possibility of endogenous synthesis of H2S in frog myocardium and regulation of its contractility by the activation of phosphodiesterases hydrolyzing cAMP, which leads to a decrease in the activation of cAMP-dependent protein kinases and phosphorylation of voltage-dependent L-type Ca channels. As a result, the reduction of calcium entry into cardiomyocytes decreases the contractility of frog myocardium. © 2013 Pleiades Publishing, Ltd

Effects of Maternal Hyperhomocysteinemia on the Early Physical Development and Neurobehavioral Maturation of Rat Offspring

© 2016, Springer Science+Business Media New York.During pregnancy, several complications have been associated with hyperhomocysteinemia (HHcy) and elevated homocysteine (Hcy) levels have been shown to play a role in the etiology of preeclampsia, placental abruption, intrauterine growth retardation, and neural tube defects and associated with the neurological consequences. In the present work, we investigated the effects of chronic maternal HHcy on the development and neurobehavioral maturation of the offspring. We analyzed classical parameters of development such as body weight, eyelid opening, ear unfolding, incisor eruption, and the appearance of hair, and subjected the pups to various tests that reflected the neurobehavioral maturation extending from 4th to 20th postnatal days (righting reflex, negative geotaxis, cliff avoidance, head shake, acoustic startle reflex, free-fall righting, cliff avoidance caused by visual stimulus, olfactory discrimination). We have shown that newborn animals were characterized by lower body weight and higher mortality. Besides, the delay in neurobehavioral maturation of the pups from the Hcy group was observed. The obtained results indicate that early developmental impairments of brain maturation induced by prenatal HHcy may underlie long-term deficits in the learning and memory behaviors

Synthesis and antiadrenergic properties of β-substituted alcohols based on 6-hydroxymethylpyridoxine

© 2016, Springer Science+Business Media New York.An approach to the synthesis of epoxides based on 6-hydroxymethylpyridoxine acetals was developed. The epoxides obtained were involved in the ring opening reactions by nitrogen-, oxygen-, and sulfur-containing nucleophiles. Cytotoxicity and antiadrenergic properties of some synthesized compounds were studied on the models in situ and in vivo

Interplay Between Hydrogen Sulfide and Adrenergic and Muscarinic Receptors in the Mouse Atrium

© 2016, Springer Science+Business Media New York.Hydrogen sulfide (H2S) is synthesized endogenously, and it has a negative inotropic effect on myocardium of different animal species. Interaction between H2S and adrenergic and muscarinic receptors in regulation of mouse atrium contractile function was investigated in this study. Sodium hydrosulfide (NaHS, 300 μM), the H2S donor, decreased the contraction force of atrium. NaHS did not affect the positive inotropic effect of β-adrenoceptors (β-AR) activation by isoproterenol (ISO, 1 μM). The effect of the H2S donor under β-AR stimulation showed no differences comparison to control values. The agonist of muscarinic receptors carbachol (1 μM) induced a negative inotropic effect and partially prevented the reduction of cardiac muscle contractility by NaHS. Moreover, the effect of carbachol was more pronounced after preliminary application of NaHS. At the same time, after inhibition of β-AR (propranolol, 1 μM) or muscarinic receptors (atropine, 1 μM), negative inotropic effect of NaHS was the same as in control conditions. These results suggest that the H2S effects are mediated by intracellular signaling pathways activated by muscarinic receptors

Interplay Between Hydrogen Sulfide and Adrenergic and Muscarinic Receptors in the Mouse Atrium

© 2016, Springer Science+Business Media New York.Hydrogen sulfide (H2S) is synthesized endogenously, and it has a negative inotropic effect on myocardium of different animal species. Interaction between H2S and adrenergic and muscarinic receptors in regulation of mouse atrium contractile function was investigated in this study. Sodium hydrosulfide (NaHS, 300 μM), the H2S donor, decreased the contraction force of atrium. NaHS did not affect the positive inotropic effect of β-adrenoceptors (β-AR) activation by isoproterenol (ISO, 1 μM). The effect of the H2S donor under β-AR stimulation showed no differences comparison to control values. The agonist of muscarinic receptors carbachol (1 μM) induced a negative inotropic effect and partially prevented the reduction of cardiac muscle contractility by NaHS. Moreover, the effect of carbachol was more pronounced after preliminary application of NaHS. At the same time, after inhibition of β-AR (propranolol, 1 μM) or muscarinic receptors (atropine, 1 μM), negative inotropic effect of NaHS was the same as in control conditions. These results suggest that the H2S effects are mediated by intracellular signaling pathways activated by muscarinic receptors

Role of calcium and potassium channels in effects of hydrogen sulfide on frog myocardial contractility

The effects of sodium hydrosulfide NaHS, a donor of hydrogen sulfide H 2S, on the force of muscle contraction were examined on isolated myocardial strips from frog ventricles. NaHS decreased the amplitude of muscle contractions in a dose-dependent manner under normal conditions and during inhibition of Ca channels with nifedipine. In contrast, under conditions of blockade of ATP-dependent potassium channels with glibenclamide, NaHS exerted a positive inotropic effect from the first minute of application. Neither blockade, nor activation of ATP-dependent K-channels with glibenclamide modulated the negative inotropic effect of NaHS. Inhibition of K-channels with tetraethylammonium (TEA) (3, 5, 10 mM) or 4-aminopyridine increased the amplitude of myocardial contractions. Preliminary application of 4-aminopyridine or TEA (3 mM) did not eliminate NaHS-induced negative inotropic effect, although higher TEA concentrations (5 or 10 mM) prevented it. The data indicate that the targets of H2S in frog myocardium are ATP-dependent, Ca-activated, and voltage-dependent K-channels. © 2011 Springer Science+Business Media, Inc

Hydrogen sulfide in regulation of frog myocardium contractility

Hydrogen sulfide (H2S) is an endogenously synthesized gaseous molecule which, along with nitric oxide and carbon monoxide, induces a number of effects in cardiovascular system under normal and pathological conditions. In the present work, the effects and underlying mechanisms of the H2S donor sodium hydrosulfide (NaHS) on the isometric force of frog myocardium contraction have been studied. NaHS at the concentration of 100 μM induced negative inotropic effect and reduced the maximum velocity of the contraction and relaxation of the isolated ventricle strips. The substrate of H2S synthesis, L-cysteine (200 μM and 1 mM), induced the same effect, while the inhibitors of cystathionin-γ-lyase, the H2S-producing enzyme in heart, β-cyanoalanine (500 μM) and propargylglycine (500 μM), increased the amplitude of contraction. Inhibition of cystathionin-γ-lyase by β-cyanoalanine prevented the negative inotropic effect of L-cysteine. After the inhibition of adenylate cyclase by MDL-12,330A (3 μM) or phosphodiesterases by IBMX (200 μM), the effect of NaHS was less than that in the control. In the presence of membrane-penetrating analogous of cAMP, 8Br-cAMP (100 μM) and pCPT-cAMP (100 μM), the negative inotropic effect of NaHS was completely retained. The effect of NaHS significantly decreased after preliminary application of the NO donor, SNAP (10 μM), and did not change after the inhibition of NO synthases by L-NAME (100 μM). The results suggest the possibility of endogenous synthesis of H2S in frog myocardium and regulation of its contractility by the activation of phosphodiesterases hydrolyzing cAMP, which leads to a decrease in the activation of cAMP-dependent protein kinases and phosphorylation of voltage-dependent L-type Ca channels. As a result, the reduction of calcium entry into cardiomyocytes decreases the contractility of frog myocardium. © 2013 Pleiades Publishing, Ltd

Role of calcium and potassium channels in effects of hydrogen sulfide on frog myocardial contractility

The effects of sodium hydrosulfide NaHS, a donor of hydrogen sulfide H 2S, on the force of muscle contraction were examined on isolated myocardial strips from frog ventricles. NaHS decreased the amplitude of muscle contractions in a dose-dependent manner under normal conditions and during inhibition of Ca channels with nifedipine. In contrast, under conditions of blockade of ATP-dependent potassium channels with glibenclamide, NaHS exerted a positive inotropic effect from the first minute of application. Neither blockade, nor activation of ATP-dependent K-channels with glibenclamide modulated the negative inotropic effect of NaHS. Inhibition of K-channels with tetraethylammonium (TEA) (3, 5, 10 mM) or 4-aminopyridine increased the amplitude of myocardial contractions. Preliminary application of 4-aminopyridine or TEA (3 mM) did not eliminate NaHS-induced negative inotropic effect, although higher TEA concentrations (5 or 10 mM) prevented it. The data indicate that the targets of H2S in frog myocardium are ATP-dependent, Ca-activated, and voltage-dependent K-channels. © 2011 Springer Science+Business Media, Inc