The purpose of this study was to determine the role of lipotoxicity in vascular smooth muscle (VSM). C1-BODIPY 500/510 C12 used to assess the ability of VSM A7r5 cells to transport long-chain fatty acids showed that lipid transport did not appear to limit metabolism. Thin layer chromatography revealed that storage of transported fatty acid occurred primarily as mono- and diglycerides and fatty acids but not as triglycerides. We used lipid-induced apoptosis as a measure of lipotoxicity and found that 1.5 mM palmitate (6.8:1) bound to albumin resulted in a 15-fold increase in the number of apoptotic cells compared to the control at 24 hours. This apoptosis did not seem to be due to an increase in reactive oxygen species (ROS) since VSM cells incubated in palmitate showed less ROS production than cells incubated in albumin only. Similar exposure to oleate did not significantly increase the number of apoptotic cells compared to the control. Oleate actually significantly attenuated the apoptosis induced by palmitate, suggesting that unsaturated fatty acids have a protective effect on cells undergoing palmitate-induced apoptosis. These results suggest that vascular smooth muscle is vulnerable to lipotoxicity and that this lipotoxicity may play a role in the development of atherosclerosis., H. M. Mattern, C. D. Hardin., and Obsahuje bibliografii a bibliografické odkazy
Vascular stenosis is often described only by its percentage in both clinical and scientific praxis. Previous studies gave inconclusive results regarding the effect of stenosis eccentricity on its hemodynamic effect. The aim of this experimental study was to investigate and quantify the effect of stenosis severity and eccentricity on the pressure drop. A combination of pressure and flow measurements by Par ticle Imaging Velocimetry (PIV) method was used. Models of the same stenosis significance but with different levels of eccentricity were studied in vitro by PIV. This study has shown that stenosis asymmetry is associated with more profound pressure drop an d flow volume decrease. On the contrary, pressure drop and flow volume decrease were not further significantly influenced by the level of asymmetry. Hemodynamic changes associated with stenosis eccentricity must be taken into account in both clinical and s cientific studies., L. Novakova, J. Kolinsky, J. Adamec, J. Kudlicka, J. Malik., and Obsahuje bibliografii
The effects of transient and sustained hyperthyroidism on vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI) levels were studied in the heart atria of developing and adult rats. Newborn rats were divided into 5 groups. Neo-T animals were treated with thyroxine (T4) during postnatal days 1-8 and sacrificed at the age of 60 days. Neo-S rats were treated with T4 during postnatal days 1-60 and sacrificed one day later. Adult-1 and Adult-2 animals received T4 during days 52-60 and were sacrificed 5-6 days and 1 day later, respectively. Control animals were injected with saline. VIP-LI concentrations were determined in extracts from the left and right atria separately. In Neo-S and Adult-2 rats, spontaneous heart rate, the weight of both atria and total T4 serum levels were significantly enhanced, while their body weight was decreased. The ratio atria weight to body weight was significantly increased in all groups except for Adult-1 animals. Hyperthyroidism led to a significant decrease in VIP-LI levels in both atria of Neo-S and Neo-T rats. Hyperthyroidism induced in adult rats also decreased VIP-LI levels in both atria. However, this change was only transient. In conclusion, our data have provided new evidence that hyperthyroidism induced during the early neonatal period interferes with the development of VIP-ergic innervation in rat atria. The period of the first few postnatal days seems to be essential for this effect, since VIP-LI concentrations in 60-day-old animals did not significantly differ between Neo-S and Neo-T atria., J. Kuncová, J. Slavíková., and Obsahuje bibliografii
Pathophysiological mechanisms underlying the development of renal dysfunction and progression of congestive heart failure (CHF) remain poorly understood. Recent studies have revealed striking differences in the rol e of epoxyeicosatrienoic acids (EETs), active products of cytochrome P-450-dependent epoxygenase pathway of arachidonic acid, in the progression of aorto-caval fistula (ACF)-induced CHF between hypertensive Ren-2 renin transgenic rats (TGR) and transgene-negative normotensive Hannover Sprague-Dawley (HanSD) controls. Both ACF TGR and ACF HanSD strains exhibited marked intrarenal EETs deficiency and impairment of renal function, and in both strains chronic pharmacologic inhibition of s oluble epoxide hydrola se (sEH) (which normally degrades EETs) normalized EETs levels. However, the treatment improved the survival rate and attenuated renal function impairment in ACF TGR only. Here we aimed to establish if the reported improved renal function and attenuation o f progression of CHF in ACF TGR observed after sEH blockade depends on increased vasodilatory responsiveness of renal resistance arteries to EETs. Therefore, we examined the responses of interlobar arteries from kidneys of ACF TGR and ACF HanSD rats to EET-A, a new stable 14,15-EET analog. We found that the arteries from ACF HanSD kidneys rats exhibited greater vasodilator responses when compared to the ACF TGR arteries. Hence, reduced renal vasodilatory responsiveness cannot be responsible for the lack of beneficial effects of chronic sEH inhibition on the development of renal dysfunction and progression of CHF in ACF HanSD rats., A. Sporková, Z. Husková, P. Škaroupková, N. Rami Reddy, J. R. Falck, J. Sadowski, L. Červenka., and Obsahuje bibliografii
The aim of this study was to test the hypothesis that vasorelaxing action of vasonatrin peptide (VNP) is due to activation of the large-conductance Ca2+-activated potassium channel (BKCa) via guanylyl cyclase (GC)-coupled natriuretic peptide receptors (NPRs) in vascular smooth muscle cells (VSMCs). Contraction experiments were performed using human radial artery, whereas BKCa current by patch clamp was recorded in cells from rat mesenteric artery. Contractility of rings cut from human radial artery was detected in vitro. As a result, VNP induced a dose-dependent vasorelaxation of human radial artery, which could be mimicked by 8-Br-cGMP, and suppressed by TEA, a blocker of BKCa, HS-142-1, a blocker of GC-coupled NPRs, or methylene blue (MB), a selective inhibitor of guanylyl cyclase. Sequentially, whole-cell K+ currents were recorded using patch clamp techniques. BKCa current of VSMCs isolated from rat mesentery artery was obtained by subtracting the whole cell currents after applications of 10-7 mol/l iberiotoxin (IBX) from before its applications. In accordance with the results of arterial tension detection, BKCa current was significantly magnified by VNP, which could also be mimicked by 8-Br-cGMP, whereas suppressed by HS-142-1, or MB. Taken together, VNP acts as a potent vasodilator, and NPRA/B-cGMP-BKCa is one possible signaling system involved in VNP induced relaxation., J. Yu ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The aim of this study is to define the possible effects of vegetable oils used as vitamin E vehicle on the electrical activity of the rat heart. To test the possible effects of vitamin E vehicles we studied the effect of i.p. injected corn oil, hazelnut oil or peanut oil on the action potential parameters recorded in both papillary and left atrial muscle strips. Four experimental groups were used. The control group was injected (i.p.) with distilled water, while the three remaining groups received injections of corn oil, hazelnut oil, or peanut oil for five weeks (in a dose of 0.4 ml/kg/day - minimum amount of oil in which vitamin E could be dissolved). We used borosilicated (15-20 MΩ) capillary electrodes and intracellular action potentials (AP) were recorded in isolated papillary and left atrium muscle strips. While administration of three different types of vegetable oil had no significant effect on AP parameters of papillary muscle, they significantly prolonged the repolarization phase of AP in atrial strips. These results show that vegetable oils used as vitamin E vehicles may alter the electrical activity of the heart in a tissue-dependent manner. The present data indicate that the possible effect of vegetable oil vehicles should be kept in mind while evaluating the possible effects of in vivo vitamin E administration., S. Ozdemir, M. Ayaz, T. Tuncer, M. Ugur, B. Turan., and Obsahuje bibliografii
To investigate the vestibular and somatosensory interaction in human postural control, a galvanic vestibular stimulation of cosine bell shape resulting in a small forward or backward body lean was paired with three vibrations of both soleus muscles. The induced body lean was registered by the position of the center of foot pressure (CoP). During a quiet stance with eyes closed the vibration of both soleus muscles with frequency (of) 40 Hz, 60 Hz and 80 Hz resulted in the body lean backward with velocities related to the vibration frequencies. The vestibular galvanic stimulation with the head turned to the right caused forward or backward modification of CoP backward response to the soleus muscles vibration and peaked at 1.5-2 s following the onset of the vibration. The effect of the paired stimulation was larger than the summation of the vestibular stimulation during the quiet stance and a leg muscle vibration alone. The enhancement of the galvanic stimulation was related to the velocity of body lean induced by the leg muscle vibration. The galvanic vestibular stimulation during a faster body movement had larger effects than during a slow body lean or the quiet stance. The results suggest that velocity of a body postural movement or incoming proprioceptive signal from postural muscles potentiate the effects of simultaneous vestibular stimulations on posture., O. Dzurková, F. Hlavačka., and Obsahuje bibliografii a bibliografické odkazy
Hypoxia stimulates ventilation, but when it is sustained, a decline in the ventilatory response is seen. The mechanism responsible for this decline lies within the CNS, but still remains unknown. In this study, we attempted to elucidate the possible role of hypoxia-induced depression of respiratory neurons by comparing the ventilatory response to hypoxia in intact rats and those with denervated carotid bodies. A whole-body plethysmograph was used to measure tidal volume, frequency of breathing and minute ventilation (VE) in awake and anesthetized intact rats and rats after carotid body denervation during exposure to hypoxia (FIO2 0.1). Fifteen-minute hypoxia induced an initial increase of VE in intact rats (to 248 % of control ventilation in awake and to 227 % in anesthetized rats) followed by a consistent decline (to 207 % and 196 % of control VE, respectively). Rats with denervated carotid bodies responded with a smaller increase in VE (to 134 % in awake and 114 % in anesthetized animals), but without a secondary decline (145 % and 129 % of control VE in the 15th min of hypoxia). These results suggest that afferentation from the carotid bodies and/or the substantial increase in ventilation are crucial for the biphasicity of the ventilatory response to sustained hypoxia and that a central hypoxic depression cannot fully explain the secondary decline in VE., H. Maxová, M. Vízek., and Obsahuje bibliografii
Ventricular assist devices (VAD ) have recently established themselves as an irreplaceable th erapeutic modality of terminal heart failure. Because of the worldwide shortage of donors, ventricular assist devices play a key role in modern heart failure therapy. Some clinical data have revealed the possibility of cardiac recovery during VAD applic ation. On the other hand, both clinical and experiment al studies indicate the risk of the cardiac atrophy development, especially after prolonged mechanical unloading. Little is known about the specific mechanisms governing the unloading-induced cardiac atrophy and about the exact ultrastructural changes in cardiomyocytes, and even less is known about the ways in which possible therapeutical interventions may affect heart at rophy. One aim of this review was to present important aspects of the development of VAD- related cardiac atrophy in humans and we also review the most significant observations linking clinical data and those derived from studies using experimental mo dels. The focus of this article was to review current methods applied to alleviate cardiac atrophy which follows mechanical unloading of the heart. Out of many pharmacological agents studied, only the selective beta2 agonist clenbuterol has been proved to have a significantly beneficial effect on unloading-induced atrophy. Mechanical means of atrophy alleviation also seem to be effective and promising., M. Pokorný ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Aims of the study were to compare the development of electrocardiographic responses of the ischemia-induced heterogeneities of activation and repolarization in the ventricular myocardium of normal and diabetic animals. Body surface ECGs and unipolar electrograms in 64 epicardial leads were recorded before and during 20 min after the ligation of the left anterior descending artery in diabetic (alloxan model, 4 weeks, n=8) and control (n=8) rabbits. Activation times (ATs), end of repolarization times (RTs) and repolarization durations (activation-recovery intervals, ARIs) were determined in ischemic and periischemic zones. In contrast to the controls, the diabetic rabbits demonstrated the significant prolongation of ATs and shortening of ARIs (P<0.05) during ischemia in the affected region resulting in the development and progressive increase of the ARI and RT gradients across the ischemic zone boundary. The alterations of global and local dispersions of the RTs in diabetics correlated with the Tpeak-Tend interval changes in the limb leads ECGs. In the ischemic conditions, the diabetic animals differed from the controls by the activation delay, significant repolarization duration shortening, and the increase of local repolarization dispersion; the latter could be assessed by the Tpeak-Tend interval measurements in the body surface ECGs., K. A. Sedova, M. A. Vaykshnorayte, A. O. Ovechkin, P. Kneppo, O. G. Bernikova, V. A. Vityazev, J. E. Azarov., and Obsahuje bibliografii