Accumulating evidence indicates that hypertension is associated with "ion channel remodeling" of vascular smooth muscle cells (VSMCs). The objective of this study was to determine the effects of exercise intensity/volume on hypertension-associated changes in large-conductance Ca2+-activated K+ (BKCa) channels in mesenteric arteries (MAs) from spontaneously hypertensive rats (SHR). Male SHRs were randomly assigned to three groups: a low-intensity aerobic exercise group (SHR-L: 14 m/min), a moderate-intensity aerobic exercise group (SHR-M: 20 m/min), and a sedentary group (SHR). Age-matched Wistar-Kyoto rats (WKYs) were used as normotensive controls. Exercise groups completed an 8-week exercise program. Elevation of the α and β1 proteins was unequal in MA myocytes from SHRs, with the β1 subunit increasing more than the α subunit. BKCa contribution to vascular tone regulation was higher in the myocytes and arteries of SHRs compared to WKYs. SHR BKCa channel subunit protein expression, β1/α ratio, whole cell current density and single-channel open probability was also increased compared with WKYs. Aerobic exercise lowered systemic blood pressure and normalized hypertension-associated BKCa alterations to normotensive control levels in the SHRs. These effects were more pronounced in the moderate-intensity group than in the low-intensity group. There is a dose-effect for aerobic exercise training in the range of low to moderate-intensity and accompanying volume for the correction of the pathological adaptation of BKCa channels in myocytes of MAs from SHR., Y. Zhang, Y. Chen, L. Zhang, N. Lu, L. Shi., and Obsahuje bibliografii
5-hydroxytryptamine (5-HT) is involved in the stress-induced alteration of colonic functions, specifically motility and secretion, but its precise mechanisms of regulation remain unclear. In the present study, we have investigated the effects of 5-HT on rat colonic mucosal secretion after acute water immersion restraint stress, as well as the underlying mechanism of this phenomenon, using short circuit current recording (ISC), real-time polymerase chain reaction, Western blot analysis, and enzyme-linked immunosorbance assays. After 2 h of water immersion restraint stress, the baseline ISC and 5-HT-induced ISC responses of the colonic mucosa were significantly increased. Pretreatment with selective 5-HT4 receptor antagonist, SB204070, inhibited the 5-HT-induced colonic ISC response by 96 % in normal rats and 91.2 % in acute-stress rats. However, pretreatment with the selective antagonist of 5-HT3 receptor, MDL72222 or Y-25130, had no obvious effect on 5-HT-induced ISC responses under either set of conditions. Total protein expression of both the mucosal 5-HT3 receptors and the 5-HT4 receptors underwent no significant changes following acute stress. Both colonic basal cAMP levels and foskolin-induced ISC responses were significantly enhanced in acute stress rats. 5-HT significantly enhanced the intracellular cAMP level via 5-HT4 receptors in the colonic mucosa from both control and stressed animals, and 5-HT-induced cAMP increase in stressed rats was not more than that in control rats. Taken together, the present results indicate that acute water immersion restraint stress enhances colonic secretory responses to 5-HT in rats, a process in which increased cellular cAMP accumulation is involved., Y. Li, L. S. Li, X. L. Zhang, Y. Zhang, J. D. Xu, J. X. Zhu., and Obsahuje bibliografii
Spontaneous activity of cortical neurons exhibits alternative fluctuations of membrane potential consisting of phased depolarization called "up-state" and persistent hyperpolarization called "down-state" during slow wave sleep and anesthesia. Here, we examined the effects of sound stimuli (noise bursts) on neuronal activity by intracellular recording in vivo from the rat auditory cortex (AC). Noise bursts increased the average time in the up-state by 0.81±0.65 s (rang e, 0.27-1.74 s) related to a 10 s recording duration. The rise times of the spontaneous up-events averaged 69.41±18.04 ms (range, 40.10-119.21 ms), while those of the sound-evoked up-events were significantly shorter (p<0.001) averaging on ly 22.54±8.81 ms (range, 9.31- 45.74 ms). Sound stimulation did not influence ongoing spontaneous up-events. Our data suggest that a sound stimulus does not interfere with ongoing spontaneous neuronal activity in auditory cortex but can evoke new depolarizations in addition to the spontaneous ones., Y. Zhang ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
In previous studies, it has been shown that recombinant human neuregulin-1(rhNRG-1) is capable of improving the survival rate in animal models of doxorubicin (DOX)-induced cardiomyopathy; however, the underlying mechanism of this phenomenon remains unknown. In this study, the role of rhNRG-1 in attenuating doxorubicin-induce apoptosis is confirmed. Neonatal rat ventricular myocytes (NRVMs) were subjected to various treatments, in order to both induce apoptosis and determine the effects of rhNRG-1 on the process. Activation of apoptosis was determined by observing increases in the protein levels of classic apoptosis markers (including cleaved caspase-3, cytochrome c, Bcl-2, BAX and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining). The activation of Akt was detected by means of western blot analysis. The study results showed that doxorubicin increased the number of TUNEL positive cells, as well as the protein levels of cleaved caspase-3 and cytochrome c, and reduced the ratio of Bcl-2/Bax. However, all of these effects were markedly antagonized by pretreament with rhNRG-1. It was then further demonstrated that the effects of rhNRG-1 could be blocked by the phosphoinositole-3-kinase inhibitor LY294002, indicating the involvement of the Akt process in mediating the process. RhNRG-1 is a potent inhibitor of doxorubicin-induced apoptosis, which acts through the PI3K-Akt pathway. RhNRG-1 is a novel therapeutic drug which may be effective in preventing further damage from occurring in DOX-induced damaged myocardium., T. An, ... [et al.]., and Obsahuje seznam literatury
C-type natriuretic peptides (CNP) play an inhibitory role in smooth muscle motility of the gastrointestinal tract, but the effect of CNP on delayed rectifier potassium currents is still unclear. This study was designed to investigate the effect of CNP on delayed rectifier potassium currents and its mechanism by using conventional whole-cell patch- clamp technique in guinea-pig gastric myocytes isolated by collagenase. CNP significantly inhibited delayed rectifier potassium currents [IK (V)] in dose-dependent manner, and CNP inhibited the peak current elicited by depolarized step pulse to 86.1±1.6 % (n=7, P<0.05), 78.4±2.6 % (n=10, P< 0.01) and 67.7±2.3 % (n=14, P<0.01), at concentrations of 0.01 μmol/l, 0.1 μmol/l and 1 μmol/l, respectively, at +60 mV. When the cells were preincubated with 0.1 μmol/l LY83583, a guanylate cyclase inhibitor, the 1 μmol/l CNP-induced inhibition of IK (V) was significantly impaired but when the cells were preincubated with 0.1 μmol/l zaprinast, a cGMP-sensitive phosphodiesterase inhibitor, the 0.01 μmol/l CNP-induced inhibition of IK (V) was significantly potentiated. 8-Br-cGMP, a membrane permeable cGMP analogue mimicked inhibitory effect of CNP on IK (V). CNP-induced inhibition of IK (V) was completely blocked by KT5823, an inhibitor of cGMP-dependent protein kinase (PKG). The results suggest that CNP inhibites the delayed rectifier potassium currents via cGMP-PKG signal pathway in the gastric antral circular myocytes of the guinea-pig., H. Y. Xu, X. Huang, M. Yang, J.-B. Sun, L.-H. Piao, Y. Zhang, L. Gao, W.-X. Xu., and Obsahuje bibliografii a bibliografické odkazy