The aim of this work was to investigate the effect of 10 weeks of lisinopril treatment to spontaneously hypertensive rats (SHRs) on day/night variations of blood pressure, heart rate and autonomic cardio-regulation parameters. Male SHR with surgically implanted radio-telemetry implant that provided direct measurements of arterial pressure and electrocardiogram wave were used. Animals were allocated to two groups (n=5 each). The first group was treated with lisinopril (20 mg/kg by gavage) daily for 10 weeks (treated group); whereas the second was gavaged daily with tap water (untreated group). Arterial blood pressure, ECG and other telemetry parameters were recorded at the start and at the end of 10-week treatment. Collected data were analyzed using specialized software and were statistically tested. In addition to the expected lowering of blood pressure, spectral analysis of R-R intervals revealed that lisinopril treatment for 10 weeks significantly caused 2-3 fold increase in heart rate variability (HRV) during both active and inactive periods. However, R-R interval durations demonstrated variable distribution patterns during those periods. The cause of observed distribution pattern of R-R intervals during active and inactive periods may be of significance to better understand HRV changes and warrants further investigations., S. Albarwani, S. Al-Siyabi, M. O. Tanira., and Obsahuje seznam literatury
Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are effective drugs in the treatment of hypercholesterolemia, however, their undesirable actions are not fully known. We investigated the effects of atorvastatin on the oxidative phosphorylation and membrane fluidity in liver mitochondria, and also on the coenzyme Q (CoQ) content in the mitochondria, liver tissue, and plasma of rats on a standard (C) and hypercholesterolemic (HCh) diet. Atorvastatin was administered at either low (10 mg⋅kg-1) or high dose (80 mg⋅kg-1) for four weeks. The high dose of the drug decreased the concentrations of total cholesterol and triacylglycerols in the plasma and liver of rats on a HCh diet. Administration of atorvastatin was associated with decreased oxygen uptake (state 3), and oxidative phosphorylation rate in the mitochondria of both C and HCh rats. Further, the drug influenced mitochondrial membrane fluidity and dose-dependently reduced concentrations of oxidized and reduced forms of CoQ in the mitochondria. Our findings point to an association between in vivo administration of atorvastatin and impaired bioenergetics in the liver mitochondria of rats, regardless of diet, in conjunction with simultaneous depletion of oxidized and reduced CoQ forms from the mitochondria. This fact may play a significant role in the development of statin-induced hepatopathy., O. Uličná ...[et al.]., and Obsahuje seznam literatury
Uric acid is involved in nitrogenous waste in animals, together with ammonia and urea. Uric acid has also antioxidant properties and is a surrogate marker of metabolic syndrome. We observed that the elevated plasma uric acid of high-fat fed mice was normalized by benzylamine treatment. Indeed, benzylamine is the reference substrate of semicarbazide-sensitive amine oxidase (SSAO), an enzyme highly expressed in fat depots and vessels, which generates ammonia when catalysing oxidative deamination. Ammonia interferes with uric acid metabolism/solubility. Our aim was therefore to investigate whether the lowering action of benzylamine on uric acid was related to an improvement of diabetic complications, or was connected with SSAO-dependent ammonia production. First, we observed that benzylamine administration lowered plasma uric acid in diabetic db/db mice while it did not modify uric acid levels in normoglycemic and lean mice. In parallel, benzylamine improved the glycemic control in diabetic but not in normoglycemic mice, while plasma urea remained unaltered. Then, uric acid plasma levels were measured in mice invalidated for AOC3 gene, encoding for SSAO. These mice were unable to oxidize benzylamine but were not diabetic and exhibited unaltered plasma uric levels. Therefore, activated or abolished ammonia production by SSAO was without influence on uric acid in the context of normoglycemia. Our observations confirm that plasma uric acid increases with diabetes and can be normalized when glucose tolerance is improved. They also show that uric acid, a multifunctional metabolite at the crossroads of nitrogen waste and of antioxidant defences, can be influenced by SSAO, in a manner apparently related to changes in glucose homeostasis., C. Carpéné ... [et al.]., and Obsahuje seznam literatury
After global cerebral hypoxia, many patients are severely disabled even after intensive neurorehabilitation. Secondary mechanisms of brain injury as a result of biochemical and physiological events occur within a period of hours to months, and provide a window of opportunity for therapeutic intervention. Erythropoietin (EPO) has been shown to be neuroprotective in the brain subjected to a variety of injuries. Fifty-nine 3-month-old male Wistar rats were randomly distributed to experimental groups with respect to the housing (enriched environment – EE, standard housing – SH), to hypoxia exposure, and to EPO treatment. An acute mountain sickness model was used as a hypobaric hypoxia simulating an altitude of 8000 m. One half of the animals received erythropoietin injections, while the others were injected saline. Spatial memory was tested in a Morris water maze (MWM). The escape latency and the path length were measured. Better spatial learning in MWM was only seen in the group that received erythropoietin together with enriched environment. EPO administration itself had no influence on spatial memory. The results were very similar for both latencies and path lengths. These results support the idea that after brain injuries, the recovery can be potentiated by EPO administration combined with neurorehabilitation., M. Hralová, ... [et al.]., and Obsahuje seznam literatury
Hypoxic pulmonary hypertension (HPH) is a syndrome characterized by the increase of pulmonary vascular tone and the structural remodeling of peripheral pulmonary arteries. Mast cells have an important role in many inflammatory diseases and they are also involved in tissue remodeling. Tissue hypoxia is associated with mast cell activation and the release of proteolytic enzymes, angiogenic and growth factors which mediate tissue destruction and remodeling in a variety of physiological and pathological conditions. Here we focused on the role of mast cells in the pathogenesis of hypoxic pulmonary hypertension from the past to the present., H. Maxová, J. Herget, M. Vízek., and Obsahuje seznam literatury
A characteristic of mast cells is the degranulation in response to various stimuli. Here we have investigated the effects of various physical stimuli in the human mast-cell line HMC-1. We have shown that HMC-1 express the transient receptor potential channels TRPV1, TRPV2 and TRPV4. In the whole-cell patchclamp configuration, increasing mechanical stress applied to the mast cell by hydrostatic pressure (–30 to –90 cm H2 O applied via the patch pipette) induced a current that could be inhibited by 10 µM of ruthenium red. This current was also inhibited by 20 µM SKF96365, an inhibitor that is among TRPV channels specific for the TRPV2. A characteristic of TRPV2 is its activation by high noxious temperature; temperatures exceeding 50 °C induced a similar ruthenium-red-sensitive current. As another physical stimulus, we applied laser light of 640 nm. Here we have shown for the first time that the application of light (at 48 mW for 20 min) induced an SKF96365-sensitive current. All three physical stimuli that led to activation of SKF96365-sensitive current also induced pronounced degranulation in the mast cells, which could be blocked by ruthenium red or SKF96365. The results suggest that TRPV2 is activated by the three different types of physical stimuli. Activation of TRPV2 allows Ca2+ ions to enter the cell, which in turn will induce degranulation. We, therefore, suggest that TRPV2 plays a key role in mast-cell degranulation in response to mechanical, heat and red laser-light stimulation., D. Zhang ... [et al.]., and Obsahuje seznam literatury
The multi-functional proteins, insulin-like growth factor-I (IGF-I) and leptin were present in seminal plasma from different species. Concentrations of IGF-I in equine and porcine semen were 20 and 17.5 ng/ml, respectively. Seminal plasma concentrations of leptin were 1 ng/ml in human and 11 ng/ml in porcine samples., B. R. Lackey, S. L. Gray, D. M. Henricks., and Obsahuje bibliografii
We have studied the mechanism of Na+ deprivation-induced catecholamine secretion from freshly isolated bovine adrenal chromaffin cells. Na+ deprivation-induced catecholamine secretion depended on free extracellular Ca2+ concentrations and was almost parallel to 45Ca2+ influx into the cells under various experimental conditions. Furthermore, Na+ deprivation-induced 45Ca2+ influx and catecholamine secretion were actually induced by a relative Na+ concentration gradient across the plasma membrane, but not by simple omission of Na+ from the medium. These results indicate that the deprivation of Na+ from the medium changes the relative Na+ gradient across the plasma membrane and results in Ca2+ influx via a reverse mode of Na+-Ca2+ exchange rather than by inducing Ca2+ entry through Ca2+ channels by eliminating the competition between extracellular Na+ and Ca2+., M. Isosaki, T. Nakashima., and Obsahuje bibliografii
The aim of this study was to investigate the effects of melatonin on oxidative stress, the expression of transient receptor potential melastatin-2 (TRPM2) in guinea pig brains, and the influence of melatonin on oxidative stress in lungs and airway inflammation induced by particulate matter 2.5 (PM2.5). A particle suspension (0.1 g/ml) was nasally administered to the guinea pigs to prepare a PM2.5 exposure model. Cough frequency and cough incubation period were determined through RM6240B biological signal collection and disposal system. Oxidative stress markers, including malondialdehyde (MDA), total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-Px), in the medulla oblongata were examined through spectrophotometer. Reactive oxygen species (ROS) were detected in the hypoglossal nucleus, cuneate nucleus, Botzinger complex, dorsal vagal complex, and airway through dihydroethidium fluorescence. Hematoxylin-eosin (HE) staining and substance P expression via immunohistochemistry revealed the inflammatory levels in the airway. TRPM2 was observed in the medulla oblongata through immunofluorescence and Western blot. The ultrastructure of the blood-brain barrier and neuronal mitochondria was determined by using a transmission electron microscope. Our study suggests that melatonin treatment decreased PM2.5-induced oxidative stress level in the brains and lungs and relieved airway inflammation and chronic cough. TRPM2 might participate in oxidative stress in the cough center by regulating cough., Z. Ji, Z. Wang, Z. Chen, H. Jin, C. Chen, S. Chai, H. Lv, L. Yang, Y. Hu, R. Dong, K. Lai., and Seznam literatury
The Spontaneously Hypertensive Heart Failure (SHHF) rat mimics the human progression of hypertension from hypertrophy to heart failure. However, it is unknown whether SHHF animals can exercise at sufficient levels to observe beneficial biochemical adaptations in skeletal muscle. Thirty-seven female SHHF and Wistar-Furth (WF) rats were randomized to sedentary (SHHFsed and WFsed) and exercise groups (SHHFex and WFex). The exercise groups had access to running wheels from 6-22 months of age. Hindlimb muscles were obtained for metabolic measures that included mitochondrial enzyme function and expression, and glycogen utilization. The SHHFex rats ran a greater distance and duration as compared to the WFex rats (P<0.05), but the WFex rats ran at a faster speed (P<0.05). Skeletal muscle citrate synthase and β-hydroxyacyl-CoA dehydrogenase enzyme activity was not altered in the SHHFex group, but was increased (P<0.05) in the WFex animals. Citrate synthase protein and gene expression were unchanged in SHHFex animals, but were increased in WFex rats (P<0.05). In the WFex animals muscle glycogen was significantly depleted after exercise (P<0.05), but not in the SHHFex group. We conclude that despite robust amounts of aerobic activity, voluntary wheel running exercise was not sufficiently intense to improve the oxidative capacity of skeletal muscle in adult SHHF animals, indicating an inability to compensate for declining heart function by improving peripheral oxidative adaptations in the skeletal muscle., R. L. Schultz, ... [et al.]., and Obsahuje seznam literatury