ABSTRACT
The present study was designed to investigate the mechanisms by which P2X7 receptors (P2X7Rs) mediate the activation of vasopressinergic neurons thereby increasing sympathetic hyperactivity in the paraventricular nucleus (PVN) of the hypothalamus of rats with acute myocardial ischemia (AMI). The left anterior descending branch of the coronary artery was ligated to induce AMI in rats. The rats were pretreated with BBG (brilliant blue G, a P2X7R antagonist), nelivaptan (a vasopressin V1b receptor antagonist), or diphenyleneiodonium (DPI) [an nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor]. Hemodynamic parameters of the heart were monitored. Myocardial injury and cardiomyocyte apoptosis were assessed. In the PVN of AMI rats, P2X7R mediated microglial activation, while reactive oxygen species (ROS) and NADPH oxidase 2 (NOX2) were higher than in the sham group. Intraperitoneal injection of BBG effectively reduced ROS production and vasopressin expression in the PVN of AMI rats. Moreover, both BBG and DPI pretreatment effectively reduced sympathetic hyperactivity and ameliorated AMI injury, as represented by reduced inflammation and apoptosis of cardiomyocytes. Furthermore, microinjection of nelivaptan into the PVN improved cardiac function and reduced the norepinephrine (AE) levels in AMI rats. Collectively, the results suggest that, within the PVN of AMI rats, P2X7R upregulation mediates microglial activation and the overproduction of ROS, which in turn activates vasopressinergic neuron-V1b receptors and sympathetic hyperactivity, hence aggravating myocardial injury in the AMI setting.
ABSTRACT
Increased microglial activation and neuroinflammation within autonomic brain regions such as the rostral ventrolateral medulla (RVLM) have been implicated in stress-induced hypertension (SIH). Prorenin, a member of the brain renin-angiotensin system (RAS), can directly activate microglia. The present study aimed to investigate the effects of prorenin on microglial activation in the RVLM of SIH rats. Rats were subjected to intermittent electric foot-shocks plus noise, this stress was administered for 2 h twice daily for 15 consecutive days, and mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were monitored. The results showed that MAP and RSNA were augmented, and this paralleled increased pro-inflammatory phenotype (M1) switching. Prorenin and its receptor (PRR) expression and the NLR family pyrin domain containing 3 (NLRP3) activation were increased in RVLM of SIH rats. In addition, PLX5622 (a microglial depletion agent), MCC950 (a NLRP3 inhibitor), and/or PRO20 (a (Pro)renin receptor antagonist) had antihypertensive effects in the rats. The NLRP3 expression in the RVLM was decreased in SIH rats treated with PLX5622. Mito-tracker staining showed translocation of NLRP3 from mitochondria to the cytoplasm in prorenin-stimulated microglia. Prorenin increased the ROS-triggering M1 phenotype-switching and NLRP3 activation, while MCC950 decreased the M1 polarization. In conclusion, upregulated prorenin in the RVLM may be involved in the pathogenesis of SIH, mediated by activation of the microglia-derived NLRP3 inflammasome. The link between prorenin and NLRP3 in microglia provides insights for the treatment of stress-related hypertension.
ABSTRACT
Objective To observe the influence of early motor cardiac rehabilitation on the life quality of acute myocardial infarction patients. Methods 30 acute myocardial infarction patients underwent percutaneous transluminal coronary intervention (PCI) were randomly divided into rehabilitative group and control group which consist of 15 patients. The rehabilitative group received the individual sports programme and health education in addition to conventional treatment and nursing. The control group was just treated by traditional way. Barthel index was used to evaluate the self-care ability and life quality. Results The rehabilitative group had significantly higher self-care ability compared with control group after 30 days' treatment[(85.48 ±6.77)points vs (69.35 ±6.46)points] (P＜0.05).The rehabilitative group could care by themselves and carry on the light physical activity. In addition, heart rehabilitatione frequency was the favorable factor for improving the life quality of acute myocardial infarction patients.Conclusion Early motor cardiac rehabilitation could effectively improve the life quality of acute myocardial infarction patients which had a wide clinical application.
ABSTRACT
Objective To study the effects of preconditioning treadmill exercise on excitatory amino vacid changes in rats after the cerebral infarction and the protective effects against cerebral isehemia brain injury. Methods Thirty Sprague-Dawley rats were used in this study. Twenty-five rats were subject to an operation to establish the animal model of middle cerebral artery occlusion and divided into a isehemia group, an 1-week ex- ercise group (trained in the 4th week) , a 2-week exercise group (trained in the 3rd and 4th weeks) and a 4- week exercise group (trained for 4 weeks) , while the remaining 5 rats were subject to sham operation, and served as the controls. After 4 weeks of experiment, all the the rats were fixed on stereotactie apparatus for the brain microdialysis of the striatum. Then the focal middle cerebral artery ischemia and reperfusion were made with thread oeclussion in rats and microdialysis technique was used to collect extraeellular fluid in each period of pre-ischemia, ischemia (40, 80 and 120 min), and reperfusion (40, 80, 120, 160, 200 and 240 min) to detect the changes of the excitatory amino acid. At the same time the infarction volume was also measured at 24 hours after ischemia-reperfusion of the brain. Results The difference between any two groups was significant with regard to the volume of cerebral infarction (P < 0.05). Two weeks and four weeks of the preconditioning treadmill exercise couled significantly reduce concentration of Glu excessively released due to the ischemia (P < 0.01). Conclusion At least two weeks of preconditioning treadmill exercise can inhibit the excessive release of the important excitatory amino acid neurotransmitter glutamate, to some extent, in the process of the subse- quent ischemic brain injury and during reperfusion, which might be one of the protective mechanisms of move- ment against the early isehemie brain injury.