The present investigation was directed to study the effect of in vitro or ex vivo NO donors, sodium nitroprusside and molsidomine, using isolated sliced adipose tissue or in the form of immobilized and perfused adipocytes on the basal and isoprenaline-stimulated lipolysis. The results demonstrated that 1) in vitro application of sodium nitroprusside to perfused adipocytes or molsidomine to sliced adipose tissues affects isoprenaline-induced lipolysis in two ways, an increase in lipolysis at low isoprenaline concentrations (which means the sensitization of adipose tissues to adrenergic effect by NO) and decreased adrenergic agonist-stimulated lipolysis at higher concentration of isoprenaline (a decrease in the maximum lipolytic effect of isoprenaline), 2) low concentrations of molsidomine alone induced lipolysis from adipose tissue which attained more than 60 % of that by isoprenaline (pD2 value for molsidomine = 11.2, while pD2 for isoprenaline = 8.17) while sodium nitroprusside did not affect the basal lipolysis significantly, 3) in vivo administration of molsidomine for 2 days reduced the maximum lipolytic effect of isoprenaline and (only non-significantly) increased the sensitivity to low doses of isoprenaline. In conclusion the present data demonstrate that NO plays an important role in adrenergic lipolysis in adipose tissues and further investigations are needed to unravel the exact role of NO in lipolysis., D. Lincová, D. Mišeková, E. Kmoníčková, N. Canová, H. Farghali., and Obsahuje bibliografii
Thiazolidinediones are insulin-sensitizing drugs acting through peroxisome proliferator- activated receptor (PPAR)-γ. The aim of our study was to evaluate the effect of 5-month treatment with PPAR-γ agonist – rosiglitazone (4 mg/day), on the circulating markers of endothelial dysfunction and to evaluate the role of changes in endocrine function of adipose tissue in this process. Biochemical and metabolic parameters, circulating adiponectin, resistin, ICAM-1, VCAM-1, E-selectin, P-selectin, PAI-1, myeloperoxidase (MPO), and matrix metalloproteinase-9 (MMP-9) concentrations were assessed in 10 women with type 2 DM before and after rosiglitazone treatment and in a control group of healthy women. At baseline, diabetic group had significantly higher serum concentrations of glucose, glycated hemoglobin, V-CAM and PAI-1 compared to control group. Adiponectin levels tended to be lower in diabetic group, while resistin concentrations did not differ from control group. Rosiglitazone treatment improved diabetes compensation, significantly reduced VCAM-1, PAI-1 and E-selectin concentrations and increased adiponectin levels, while it did not affect serum resistin concentrations. Adiponectin concentrations at baseline were inversely related to E-selectin and MPO levels, this correlation disappeared after rosiglitazone treatment. We conclude that 5-month rosiglitazone treatment significantly reduced several markers of endothelial dysfunction. This effect could be at least in part attributable to marked increase of circulating adiponectin levels., R. Doležalová, M. M. Haluzík, L. Bošanská, Z. Lacinová, Z. Kasalová, T. Štulc, M. Haluzík., and Obsahuje bibliografii a bibliografické odkazy
Baclofen is the only clinically available metabotropic GABAB receptor agonist. In our experiment, we tested the hypothesis that long-term baclofen administration can impair learning and memory in rats. The experiment consisted of three parts. In the first part of the study the drug was administered simultaneously with the beginning of the behavioral tests. In the second and third part of the experiment baclofen was administered daily for 14 days and for one month before the tests. In each part of the experiment, adult rats were randomly divided into four treatment groups. Three groups were given an injection of baclofen at doses of 1 mg/kg, 5 mg/kg, 10 mg/kg, while the fourth group was injected with saline. The injections were given after each session. Spatial learning and memory were tested using the Morris water maze, involving three types of tests: Acquisition, Probe, and Re-acquisition. This work reveals that baclofen did not affect spatial learning at any of the tested doses and regardless of the length of administration. Memory was observed to be affected, but only at the highest dose of baclofen and only temporarily. This conclusion is in line with previously published clinical cases., M. Holajová, M. Franěk., and Seznam literatury
Benzodiazepines seem to be frequently abused in conjunction with opioids. Fluoxetine was reported to block morphine locomotor sensitization in rats. Sensitization has been implicated in some aspects of drug abuse. We have investigated the effect of alprazolam (0.25 mg/kg) and fluoxetine (5 mg/kg) on the development and expression of sensitization to the locomotor stimulant effect of morphine (10 mg/kg) in mice. Sensitization was produced by daily injections of morphine (10 mg/kg) for 10 days. There was a clear sensitization of locomotor activity produced by morphine in photocell activity cages but co-administration of alprazolam with morphine had no effect on the degree of sensitization. Alprazolam was also without effect on the expression of the sensitized response to morphine in mice sensitized with morphine alone. Fluoxetine partly reduced both the development and expression of morphine sensitization. In conclusion, the present experiments have not yielded evidence that alprazolam may influence the development or the expression of sensitization to morphine. However, they have corroborated and extended results indicating that fluoxetine can attenuate, to a certain level, the development and expression of morphine sensitization., M. Votava, M. Kršiak, V. Moravec., and Obsahuje bibliografii
The relationships between exercise and metabolites as well as between exercise and sarcoplasmic reticulum function were studied in gastrocnemius muscle of ovariectomized-trained rats. Prolonged moderate-intensity exercise, treadmill up-hill run for 90 min with a 10° incline, decreased the muscle glycogen content. Exercise until exhaustion further lowered the glycogen concentration to 13 % of the control, together with a significant decrease of ATP and glucose-6-phosphate concentrations. Also, Ag+-induced Ca2+release, measured in whole muscle homogenate, showed a 30 % reduction on exhaustion, while Ca2+ uptake was unaffected by this exercise. ATPase activities, of both homogenate and SR vesicles, and Ca2+ transport in the latter preparation were not altered on exhaustion. It could be concluded from these results that muscular fatigue in ovariectomized rats after aerobic exercise is caused by the change in energy supply and Ca2+ release from the SR, this latter possibly due to metabolites generated by the exercise., I. Gigli, L. E. Bussmann., and Obsahuje bibliografii
Toxic influence of high oxygen concentration on pulmonary function and structures has been known for many years. However, the influence of high oxygen concentration breathing on defensive respiratory reflexes is still not clear. In our previous experiments, we found an inhibitory effect of 100 % oxygen breathing on cough reflex intensity in healthy guinea pigs. The present study was designed to detect the effects of hyperoxia on cough reflex in guinea pigs with allergic airway inflammation. In the first phase of our experiment, the animals were sensitized with ovalbumin. Thirty-two sensitized animals were used in two separate experiments according to oxygen concentration breathing: 100 % or 50 % oxygen for 60 h continuously. In each experiment, one group of animals was exposed to hyperoxia, another to ambient air. The cough reflex was induced both by aerosol of citric acid before sensitization, then in sensitized animals at 24 h and 60 h of exposition to oxygen/air in awake animals, and by mechanical stimulation of airway mucosa in anesthetized animals just after the end of the experiment. In contrast to 50 % oxygen, 100 % oxygen breathing leads to significant decrease in chemically induced cough in guinea pigs with allergic inflammation. No significant changes were present in cough induced by mechanical stimulation of airways., M. Brozmanová, J. Hanáček, M. Tatár, A. Strapková, P. Szépe., and Obsahuje bibliografii
The present experiments were performed to evaluate if increased heart tissue concentration of fatty acids, specifically myristic, palmitic and palmitoleic acids that are believed to promote physiological heart growth, can attenuate the progression of unloading-induced cardiac atrophy in rats with healthy and failing hearts. Heterotopic abdominal heart transplantation (HTx) was used as a model for heart unloading. Cardiac atrophy was assessed from the ratio of the native- to-transplanted heart weight (HW). The degree of cardiac atrophy after HTx was determined on days 7, 14, 21 and 28 after HTx in recipients of either healthy or failing hearts. HTx of healthy hearts resulted in 23±3, 46±3, 48±4 and 46±4 % HW loss at the four time-points. HTx of the failing heart resulted in even greater HW losses, of 46±4, 58±3, 66±2 and 68±4 %, respectively (P<0.05). Activation of “fetal gene cardiac program” (e.g. beta myosin heavy chain gene expression) and “genes reflecting cardiac remodeling” (e.g. atrial natriuretic peptide gene expression) after HTx was greater in failing than in healthy hearts (P<0.05 each time). Exposure to isocaloric high sugar diet caused significant increases in fatty acid concentrations in healthy and in failing hearts. However, these increases were not associated with any change in the course of cardiac atrophy, similarly in healthy and post-HTx failing hearts. We conclude that increasing heart tissue concentrations of the fatty acids allegedly involved in heart growth does not attenuate the unloading-induced cardiac atrophy., M. Pokorný, I. Mrázová, J. Malý, J. Pirk, I. Netuka, Z. Vaňourková, Š. Doleželová, L. Červenková, H. Maxová, V. Melenovský, J. Šochman, J. Sadowski, L. Červenka., and Seznam literatury
Pioglitazone (PIO) is a thiazolidindione antidiabetic agent which improves insulin sensitivity and reduces blood glucose in experimental animals and treated patients. At the cellular level the actions of PIO in diabetic heart are poorly understood. A previous study has demonstrated shortened action potential duration and inhibition of a variety of transmembrane currents including L-type Ca2+ current in normal canine ventricular myocytes. The effects of PIO on shortening and calcium transport in ventricular myocytes from the Goto-Kakizaki (GK) type 2 diabetic rat have been investigated. 10 min exposure to PIO (0.1-10 μM) reduced the amplitude of shortening to similar extents in ventricular myocytes from GK and control rats. 1 μM PIO reduced the amplitude of the Ca2+ transients to similar extents in ventricular myocytes from GK and control rats. Caffeine-induced Ca2+ release from the sarcoplasmic reticulum and recovery of Ca2+ transients following application of caffeine and myofilament sensitivity to Ca2+ were not significantly altered in ventricular myocytes from GK and control rats. Amplitude of L-type Ca2+ current was not significantly decreased in myocytes from GK compared to control rats and by PIO treatment. The negative inotropic effects of PIO may be attributed to a reduction in the amplitude of the Ca2+ transient however, the mechanisms remain to be resolved., K. A. Salem, V. Sydorenko, M. Qureshi, M. Oz, F. C. Howarth., and Seznam literatury
Arterial compliance (AC) is an index of the elasticity of large arteries. Endothelial dysfunction has been reported to result in reduced arterial compliance, which represents increased arterial stiffness. A reduction in AC is elicited by high-intensity resistance training, however the mechanisms are obscure. Because a single bout of resistance exercise causes a transient increase in circulating plasma endothelin-1 in humans, some vasoconstrictors may play a role in the mechanisms. The present study aimed to investigate whether resistance training-induced decrease in AC is associated with changes in circulating vasoconstrictors levels in young men. Young sedentary men were assigned to control (n=5) or training (n=9) groups. The training group performed four-week high-intensity resistance training (weight training exercise; three sessions/week). We measured AC and plasma levels of endothelin-1, angiotensin II, and norepinephrine before and after intervention. Resistance training significantly decreased AC, whereas the changes in plasma levels of neither endothelin-1, nor angiotensin II, nor norepinephrine were significantly different between the control and the training groups. Moreover, we found no significant correlations between changes in circulating plasma levels (endothelin-1, angiotensin II, and norepinephrine) and in the AC. Despite of no alteration of the resting circulating plasma levels (endothelin-1, etc.), we cannot exclude a possibility that the tissue/local concentrations of vasoconstrictors (endothelin-1, etc.) around the vessels might be increased and also involved in a reduction of AC in the training group. Taken together, the present results suggest that circulating vasoconstrictors (endothelin-1, etc.) in plasma are not involved in a reduction in AC by the resistance training., K. Tagawa, S.-G. Ra, H. Kumagai, T. Yoshikawa, Y. Yoshida, K. Takekoshi, S. Sakai, T. Miyauchi, S. Maeda., and Seznam literatury
An increased risk of myocardial ischemic changes was demonstrated in patients suffering from panic disorder (PD). Using classical ECG methods, this risk cannot be evaluated in most patients. We measured the vectocardiogram (VCG) using Frank orthogonal leads and body surface maps (BSM) including 12-lead ECG. In our study of 11 PD patients (2 men, 9 women), without any seizures and pharmacological treatment and without cardiovascular symptoms, we found marked sinus tachycardia (heart rate 90.1±12.2 min-1) and a shorter R-R interval (678±93.6 ms) than in 27 controls (heart rate 73.6±7.7min-1, R-R 822.7±86.4 ms) (5 men, 22 women) (p<0.001). The VCG measured spatial QRS-STT angle was more opened (70.3±24.5°) than in the control group (49.5±19.5°) (p<0.05). The maximum (extremum) in depolarization (DIAM max 30, 40) and repolarization (RIAM max 35) of body surface isoarea and isointegral (RIIM max) maps was less positive (p<0.001) and the minimum (DIAM min 40) was less negative than in the controls (p<0.05) even in the period free of a panic attack. Our results showed the changes in the heart electric field parameters occurred in PD patients when compared to the control group., K. Pišvejcová, I. Paclt, J. Slavíček, O. Kittnar, A. Dohnalová, E. Kitzlerová., and Obsahuje bibliografii