The concentration-dependence of tert-butyl hydroperoxide (BHP) inhibitory effect on oxygen consumption in isolated rat liver mitochondria was measured in the presence of various respiratory substrates. Strong inhibitory effect at low concentrations of BHP (15-30 μM) was found for oxoglutarate and palmitoyl carnitine oxidation. Pyruvate and glutamate oxidation was inhibited at higher concentrations of BHP (100-200 μM). Succinate oxidation was not affected even at 3.3 mM BHP. Determination of mitochondrial membrane potential has shown that in the presence of NADH-dependent substrates the membrane potential was dissipated by BHP but was completely restored after addition of succinate. Our data thus indicate that beside peroxidative damage of complex I also various mitochondrial NADH-dependent dehydrogenases are inhibited, but to a different extent and with different kinetics. Our data also show that succinate could be an important nutritional substrate protecting hepatocytes during peroxidative damage., R. Endlicher ... [et al.]., and Obsahuje seznam literatury
Diabetes mellitus is relatively frequently associated with fatty liver disease. Increased oxidative stress probably plays an important role in the development of this hepatopathy. One of possible sources of reactive oxygen species in liver is peroxisomal system. There are several reports about changes of peroxisomal enzymes in experimental diabetes, mainly enzymes of fatty acid oxidation. The aim of our study was to investigate the possible changes of activities of liver peroxisomal enzymes, other than enzymes of beta-oxidation, in experimental diabetes mellitus type 2. Biochemical changes in liver of experimental animals suggest the presence of liver steatosis. The changes of serum parameters in experimental group are similar to changes in serum of patients with non-alcoholic fatty liver disease. We have shown that diabetes mellitus influenced peroxisomal enzymes by the different way. Despite of well-known induction of peroxisomal beta-oxidation, the activities of catalase, aminoacid oxidase and NADH-cytochrome b5 reductase were not significantly changed and the activities of glycolate oxidase and NADP-isocitrate dehydrogenase were significantly decreased. The effect of diabetes on liver peroxisomes is probably due to the increased supply of fatty acids to liver in diabetic state and also due to increased oxidative stress. The changes of metabolic activity of peroxisomal compartment may participate on the development of diabetic hepatopathy., L. Turecký, V. Kupčová, E. Uhlíková, V. Mojto., and Obsahuje bibliografii
The objective of the current study was to search for genetic determinants associated with antihypertensive effects of angiotensin-converting enzyme (ACE) inhibitor captopril. Linkage and correlation analyses of captopril-induced effects on blood pressure (BP) with renal transc riptome were performed in the BXH/HXB recombinant inbred (RI) strains derived from spontaneously hypertensive rat (SHR) and Brown Norway (BN-Lx) progenitors. Variability of blood pressure lowering effects of captopril among RI strains was continuous suggesting a polygenic mode of inheritance. Linkage analysis of captopril- induced BP effects revealed a significant quantitative trait locus (QTL) on chromosome 15. This QTL colocalized with cis regulated expression QTL (eQTL) for the Ednrb (endothelin receptor type B) gene in the kidney (SHR allele was associated with increased renal expression) and renal expression of Ednrb correlated with captopril-induced BP effects. These results suggest that blood pressure lowering effects of ACE inhibitor captopril may be modulated by the variants at the Ednrb locus., J. Zicha ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
High levels of catecholamines in pheochromocytoma (PHEO) are associated with risk of cardiovascular complications. In this study, we looked for potential differences in markers of oxidative stress – vitamin C, superoxide dismutase (SOD) and malondialdehyde (MDA) in PHEO before and after the operation. We studied 18 subjects with PHEO who were examined before and approximately one year after the successful tumor removal (free of disease). All subjects had elevated urinary epinephrine and/or norepinephrine levels before the operation. Vitamin C levels increased significantly after the operation from 61±27 to 77±20 μmol/l (P=0.02), and MDA decreased significantly after the tumor removal from 2.6±0.4 to 2.0±0.6 μmol/l (P=0.01). However, no changes were found in SOD activity before and after the operation. In conclusion, increased catecholamine production in PHEO is accompanied by decreased levels of vitamin C and increased levels of MDA which may indicate the activation of oxidative stress in PHEO. Successful operation was associated with lowering of oxidative stress by using both biomarkers. On the contrary, no changes in SOD activity before and after the tumor removal were noted., H. Turková, ... [et al.]., and Obsahuje seznam literatury
We evaluated the effect of glucagon on cardiac automaticity as well as the possible role of cyclic nucleotide phosphodiesterases (PDE) in regulating this effect. Concentration response curves for glucagon in the absence and in th e presence of the non-selective PDE inhibitor IBMX were performed in the isolated right ventricle of the rat. We found that glucagon produces only a minor increase of ventricular automa ticity (11.0±4.1, n=5) when compared to the full agonist of β-adrenoceptor isoproterenol (182.2±25.3, n=7). However, IBMX enhances the maximal efficacy of glucagon on cardiac automaticity (11.0±4.1, in the absence and 45.3±3.2 in the presence of IBMX, n=5, P<0.05). These results indicate that PDE blunts proarrhythmic effects of glucagon in rat myocardium., C. Gonzalez-Muñoz, J. Hernández., and Obsahuje bibliografii a bibliografické odkazy
Phosphorylation of phospholemman (PLM) on ser68 has been proposed to at least partially mediate cyclic AMP (cAMP) mediated relaxation of arterial smooth muscle. We evaluated the time course of the phosphorylation of phospholemman (PLM) on ser68, myosin regulatory light chains (MRLC) on ser19, and heat shock protein 20 (HSP20) on ser16 during a transient forskolin-induced relaxation of histamine-stimulated swine carotid artery. We also evaluated the dose response for forskolin- and nitroglycerin-induced relaxation in phenylephrine-stimulated PLM-/- and PLM+/+ mice. The time course for changes in ser19 MRLC dephosphorylation and ser16 HSP20 phosphorylation was appropriate to explain the forskolin-induced relaxation and the recontraction observed upon washout of forskolin. However, the time course for changes in ser68 PLM phosphorylation was too slow to explain forskolin-induced changes in force. There was no difference in the phenylephrine contractile dose response or in forskolin-induced relaxation dose response observed in PLM-/- and PLM+/+ aortae. In aortae precontracted with phenylephrine, nitroglycerin induced a slightly, but significantly greater relaxation in PLM-/- compared to PLM+/+ aortae. These data are consistent with the hypothesis that ser19 MRLC dephosphorylation and ser16 HSP20 phosphorylation are involved in forskolin-induced relaxation. Our data sugge st that PLM phosphorylation is not significantly involved in forskolin-induced arterial relaxation., M. K. Meeks, S. Han, A, L. Tucker, C. M. Rembold., and Obsahuje bibliografii a bibliografické odkazy
The effects of blocking ventromedial hypothalamic nucleus (VMH) muscarinic cholinoceptors on cardiovascular responses were investigated in running rats. Animals were anesthetized with pentobarbital sodium and fitted with bilateral cannulae into the VMH. After recovering from surgery, the rats were familiarized to running on a treadmill. The animals then had a polyethylene catheter implanted into the left carotid artery to measure blood pressure. Tail skin temperature (Ttail), heart rate, and systolic, diastolic and mean arterial pressure were measured after bilateral injections of 0.2 μl of 5 × 10−9 mol methylatropine or 0.15 M NaCl solution into the hypothalamus. Cholinergic blockade of the VMH reduced time to fatigue by 31% and modified the temporal profile of cardiovascular and Ttail adjustments without altering their maximal responses. Mean arterial pressure peak was achieved earlier in methylatropine-treated rats, which also showed a 2-min delay in induction of tail skin vasodilation, suggesting a higher sympathetic tonus to peripheral vessels. In conclusion, muscarinic cholinoceptors within the VMH are involved in a neuronal pathway that controls exercise-induced cardiovascular adjustments. Furthermore, blocking of cholinergic transmission increases sympathetic outflow during the initial minutes of exercise, and this higher sympathetic activity may be responsible for the decreased performance., S. P. Wanner ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Whole-body vibration (WBV) is a new exercise method, with good acceptance among sedentary subjects. The metabolic response to WBV has not been well documented. Three groups of male subjects, inactive (SED), endurance (END) and strength trained (SPRINT) underwent a session of side-alternating WBV composed of three 3-min exercises (isometric half-squat, dynamic squat, dynamic squat with added load), and repeated at three frequencies (20, 26 and 32 Hz). VO2, heart rate and Borg scale were monitored. Twenty-seven healthy young subjects (10 SED, 8 SPRINT and 9 END) were included. When expressed in % of their maximal value recorded in a treadmill test, both the peak oxygen consumption (VO2) and heart rate (HR) attained during WBV were greatest in the SED, compared to the other two groups (VO2: 59.3 % in SED vs 50.8 % in SPRINT and 48.0 % in END, p<0.01; HR 82.7 % in SED vs 80.4 % in SPRINT and 72.4 % in END, p<0.05). In conclusions, the heart rate and metabolic response to WBV differs according to fitness level and type, exercise type and vibration frequency. In SED, WBV can elicit sufficient cardiovascular response to benefit overall fitness and thus be a potentially useful modality for the reduction of cardiovascular risk., B. Gojanovic, F. Feihl, G. Gremion, B. Waeber., and Obsahuje bibliografii
Early recognition of collapsing hemodynamics in pulmonary embolism is necessary to avoid cardiac arrest using aggressive medical therapy or mechanical cardiac support. The aim of the study was to identify the maximal acute hemodynamic compensatory steady state. Overall, 40 dynamic obstructions of pulmonary artery were performe d and hemodynamic data were collected. Occlusion of only left or right pulmonary artery did not lead to the hemodynamic collapse. When gradually obstructing the bifurcation, the right ventri cle end-diastolic area expanded proportionally to pulmonary artery mean pressure from 11.6 (10.1, 14.1) to 17.8 (16.1, 18.8) cm 2 (p<0.0001) and pulmonary artery mean pressure increased from 22 (20, 24) to 44 (41, 47) mmHg (p<0.0001) at the poin t of maximal hemodynamic compensatory steady state. Sim ilarly, mean arte rial pressure decreased from 96 (87, 101) to 60 (53, 78) mmHg (p<0.0001), central venous pressure increased from 4 (4, 5) to 7 (6, 8) mmHg (p<0.0001), heart rate increased from 92 (88, 97) to 147 (122, 165) /min (p<0.0001), contin uous cardiac output dropped from 5.2 (4.7, 5.8) to 4.3 (3.7, 5.0) l/min (p=0.0023), modified shock index increased from 0.99 (0.81, 1.10) to 2.31 (1.99, 2.72), p<0.0001. In conclusion, in stead of continuous cardiac output all of the analyzed parameters can sensitively determine the individual maximal compensatory response to obstructive shock. We assume their monitoring can be used to predict the critical phase of the hemodynamic status in routine practice., J. Kudlička ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy