Regulatory volume decrease (RVD) is essential for the survival of animal cells. The aim of this study was to observe the RVD process in rat ventricular myocytes, and to determine if the KATP channels are involved in the RVD process in these cells. By using reverse transcriptase polymerase chain reaction and Western blot analysis, we demonstrated that there are two types of KATP channels expressed in rat ventricular myocytes: Kir6.1 and Kir6.2. When rat cardiac myocytes were exposed to hypotonic solution, cell volume increased significantly within 15 min and then gradually recovered. This typical RVD process could be inhibited by a Cl– channel blocker (0.5 mM 9-anthracene-carboxylic acid , 9-AC), a K+ channel blocker (5.0 mM CsCl) and a KATP channel blocker glibenclamide (10 μM). Electrophysiological results showed that hypotonic solution activated a whole-cell current, which had similar biophysical characteristics with KATP opener (pinacidil)-induced currents. This current could be blocked by glibenclamide. Our data suggested that the RVD process in rat ventricular myocytes is dependent on the activation of K+ channels, and that KATP channels are involved in this process., L. Shi ... [et al.]., and Obsahuje seznam literatury
Measurements of ryanodine receptor (RyR) activity during dynamic changes of calcium concentration have suggested that RyR has at least four calcium binding sites, and that activation transpires as an increase in the activity within the high open probability H-mode. Binding of several Ca2+ ions within the H-mode should manifest itself in the steady-state RyR activity by the presence of multiple closed times. However, previously only two closed times were detected in the H-mode of RyR activity. Here we recorded steady-state activity of single cardiac RyRs with high temporal resolution and compared it to data simulated under the same conditions using our previously published model of RyR gating. At a 10 kHz resolution, the closed time histograms of both experimental and simulated data had three exponential components. The closed times of simulated data were not significantly different from those obtained experimentally. After filtering at 2 kHz, only two exponential closed time components with time constants not significantly different from those previously published could be detected in both experimental and simulated records. The conformity of the steady-state experimental data to the model derived from the dynamic data provides further support for the idea that RyRs need binding of multiple Ca2+ ions to open., M. Dura, I. Zahradník, A. Zahradníková., and Obsahuje bibliografii
MK-801 impaired social recognition potency of adult male rats when given immediately after the initial interaction with a juvenile rat. Administration of kynurenic acid prior to the initial interaction protected the adults against recognition deficits induced by MK-801. When re-exposed at a delay of 30 min to the familiar juvenile, social investigation in the adults was significantly reduced. Thus, the adults are able to remember olfactory stimuli emitted by juvenile con-specifics., Z. Hliňák, I. Krejčí., and Obsahuje bibliografii
Chronic hypoxia induces an increased production of nitric oxide (NO) in pulmonary prealveolar arterioles. Bioavailability of the NO in the pulmonary vessels correlates with concentration of L-arginine as well as ac tivity of phosphodiesterase-5 enzyme (PDE- 5). We tested a hypothesis whet her a combination of L-arginine and PDE-5 inhibitor sildenafil has an additive effect in reduction of the hypoxic pulmonary hypertension (HPH) in rats. Animals were exposed to chronic normobaric hypoxia for 3 weeks. In the AH group, rats were administered L-arginine during chronic hypoxic exposure. In the SH group, rats were administered sildenafil during chronic hypoxic exposure. In the SAH group, rats were treated by the combination of L-arginine as well as sildenafil during exposure to chronic hypoxia. Mean PAP, structural remodeling of peripheral pu lmonary arterioles (%DL) and RV/LV+S ratio was significantl y decreased in the SAH group compared to hypoxic controls even decreased compared to the AH and the SH groups in first two measured parameters. Plasmatic concentration of cGMP and NOx were significantly lower in the SAH group compared to hypoxic controls. We demonstrate that NO synthase substrate L-arginine and phosphodiesterase-5 inhibitor sildenafil administered in combination are more potent in attenuation of the HPH compared to a treatment by substances given alone., H. Al-Hiti ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Previous studies in our laboratory reported L-malate as a free radical scavenger in aged rats. To investigate the antioxidant mechanism of L-malate in the mitochondria, we analyzed the change in gene expression of two malate-aspartate shuttle (MAS)-related carried proteins (A GC, aspartate/glutamate carrier and OMC, oxoglutarate/malate carrier) in the inner mitochondrial membrane, and three antioxidant enzymes (CAT, SOD, and GSH-Px) in the mitochondria. The changes in gene expression of these proteins and enzymes were examined by real-time RT-PCR in the heart and liver of aged rats treated with L-malate. L-malate was orally administered in rats continuously for 30 days using a feeding atraumatic needle. We found that the gene expression of OMC and GSH-Px mRNA in the liver increased by 39 % and 38 %, respectively, in the 0.630 g/kg L-malate treatment group than that in the control group. The expression levels of SOD mRNA in the liver increased by 39 %, 56 %, and 78 % in the 0.105, 0.210, and 0.630 g/kg L-malate treatment groups, respectively. No diffe rence were observed in the expression levels of AGC, OMC, CAT, SOD, and GSH-Px mRNAs in the heart of rats between the L-malate treatment and control groups. These results predicted that L-malate may increase the antioxidant capacity of mitochondr ia by enhancing the expression of mRNAs involved in the MAS and the antioxidant enzymes., X: Zeng, J. Wu, Q. Wu, J. Zhang., and Obsahuje bibliografii
The intracellular levels of antioxidant and free radical scavenging enzymes are gradually altered during the aging process. An age-dependent increase of oxidative stress occurring throughout the lifetime is hypothesized to be the major cause of aging. The current study examined the effects of L-malate on oxidative stress and antioxidative defenses in the liver and heart of aged rats. Sprague-Dawley male rats were randomly divided into four groups, each group consisting of 6 animals. Group Ia and Group IIa were young and aged control rats. Group Ib and Group IIb were young and aged rats treated with L-malate (210 mg/kg body weight per day). L-malate was orally administrated via intragastric canula for 30 days, then the rats were sacrificed and the liver and heart were removed to determine the oxidant production, lipid peroxidation and antioxidative defenses of young and aged rats. Dietary L-malate reduced the accumulation of reactive oxygen species (ROS) and significantly decreased the level of lipid peroxidation in the liver and heart of the aged rats. Accordingly, L-malate was found to enhance the antioxidative defense system with an increased activity of antioxidant enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase (GPx) and increased glutathione (GSH) levels in the liver of aged rats, a phenomenon not observed in the heart of aged rats. Our data indicate that oxidative stress was reversed and the antioxidative defense system was strengthened by dietary supplementation with L-malate., J.-L. Wu, Q.-P. Wu, X.-F. Yang, M.-K. Wei, J.-M. Zhang, Q. Huang, X.-Y. Zhou., and Obsahuje bibliografii a bibliografické odkazy
Reactive oxygen species (ROS) have been implicated in the mechanism of postischemic contractile dysfunction, known as myocardial stunning. In this study, we examined protective effects of antioxidant enzymes, superoxide dismutase (SOD) and catalase, against ischemia/reperfusion-induced cardiac dysfunction and inhibition of Na+,K+-ATPase activity. Isolated Langendorff-perfused rabbit hearts were subjected to 15 min of global normothermic ischemia followed by 10 min reperfusion. The hearts treated with SOD plus catalase did not show significant recovery of left ventricular (LV) end-diastolic pressure compared with untreated ischemic reperfused hearts. Treatment with antioxidants had no protective effects on developed LV pressure or its maximal positive and negative first derivatives (±LVdP/dt). Myocardial stunning was accompanied by significant loss in sarcolemmal Na+,K+-ATPase activity and thiol group content. Inhibition of enzyme activity and oxidation of SH groups were not prevented by antioxidant enzymes. These results suggest that administration of SOD and catalase in perfusate do not protect significantly against cardiac dysfunction in stunned rabbit myocardium., P. Kaplán, M. Matejovičová, P. Herijgers, W. Flameng., and Obsahuje bibliografii a bibliografické odkazy