The aim of the present study was to test the hypothesis that chronic hypoxia would aggrav ate hypertension in Ren-2 transgenic rats (TGR), a well-defined monogenetic model of hypertension with increased ac tivity of endogenous renin- angiotensin system (RAS). Systolic blood pressure (SBP) in conscious rats and mean arterial pressure (MAP) in anesthetized TGR and normotensive Hannover Sprague-Dawley (HanSD) rats were determined under normoxia that was either continuous or interrupted by two weeks' hypoxi a. Expression, activities and concentrations of individual components of RAS were studied in plasma and kidney of TGR and HanSD rats under normoxic conditions and after exposure to chronic hypoxia. In HanSD rats two weeks' exposure to chroni c hypoxia did not alter SBP and MAP. Surprisingly, in TGR it de creased markedly SBP and MAP; this was associated with substantial reduction in plasma and kidney renin activities and also of angiotensin II (ANG II) levels, without altering angiotensin-converting enzyme (ACE) activities. Simultaneously, in TGR the exposu re to hypoxia increased kidney ACE type 2 (ACE2) activity and angiotensin 1-7 (ANG 1-7) concentrations as compared with TGR under continuous normoxia. Based on these results, we propose that suppression of the hypertensiogenic ACE-ANG II axis in the circulation and kidney tissue, combined with augmentation of the intrarenal vasodilator ACE2-ANG 1-7 axis, is the main mechanism responsible for the blood pressure-lowering effects of chronic hypoxia in TGR., L. Červenka, J. Bíbová, Z. Husková, Z. Vańourková, H. J. Kramer, J. Herget, Š. Jíchová, J. Sadowski, V. Hampl., and Obsahuje bibliografii
Restraint-based comparative modeling was used for calculation and visualization of the H4-H5-loop of Na+/K+-ATPase from mouse brain (Mus musculus, adult male brain, α2-isoform) between the amino acid residues Cys336 and Arg758 in the E1 conformation The structure consists of two well separated parts. The N-domain is formed by a seven-stranded antiparallel β-sheet with two additional β-strands and five α-helices sandwiching it, the P-domain is composed of a typical Rossman fold. The ATP-binding site was found on the N-domain to be identical in both α2- and α1-isoforms. The phosphorylation Asp369 residue was found in the central part of the P-domain, located at the C-terminal end of the central β-sheet. The distance between the α-carbon of Phe475 at the ATP-binding site and the α-carbon of Asp369 at the phosphorylation site is 3.22 nm. A hydrogen bond between the oxygen atom of Asp369 and the nitrogen atom of Lys690 was clearly detected and assumed to play a key role in maintaining the proper structure of the physphorylaton site in E1 conformation., G. Tejral, L. Koláčná, A. Kotyk, E. Amler., and Obsahuje bibliografii
Previously, the changes in phagocyte functions such as adherence, chemotaxis or TNFa production were found to be associated with oxidative stress in endotoxin-induced septic shock. However, in this type of oxidative stress the lymphocyte involvement has rarely been studied. In the present report, we analyzed the above functions in peritoneal lymphocytes from male and female BALB/c mice with a lethal endotoxic shock caused by intraperitoneal injection of E. coli lipopolysaccharide (LPS) (100 mg/kg), male and female Swiss mice with lethal endotoxic shock caused by intraperitoneal injection of LPS (150 and 250 mg/kg, respectively) or non-lethal endotoxic shock (100 mg/kg). In peritoneal lymphocytes obtained at 0, 2, 4, 12 or 24 h after LPS injection, the first two functions of these cells in the immune response, i.e. adherence to tissues and directed migration (chemotaxis), were studied. At 0, 0.5, 1, 1.5, 2, 4, 12 and 24 h after LPS injection, TNFa released by lymphocytes was also analyzed. The results show that endotoxic shock increases the adherence and TNFa release, and decreases the chemotaxis of peritoneal lymphocytes. These changes were more significant in mice with lethal than with non-lethal endotoxic shock, a fact that confirms the important role of lymphocytes during endotoxic shock., V. M. Víctor, D. Rubio, M. De la Fuente., and Obsahuje bibliografii
Recently an expert consensus document advised to standardize user procedures and a new cut-off value for carotid-femoral pulse wave velocity in daily practice. Our aim was to observe aortic pulse wave velocity (PWVao) and augmentation index (AIXao) in two high cardiovascular risk groups: patients with verified coronary artery disease (CAD) or with type 2 diabetes mellitus (T2DM). We also aimed to determine the cut-off values for PWVao, AIXao in CAD and T2DM patients using oscillometric device (Arteriograph). We investigated 186 CAD and 152 T2DM patients. PWVao and AIXao increased significantly in the CAD group compared to the age-, gender-, blood pressure-, and heart rate-matched control group (10.2±2.3 vs. 9.3±1.5 m/s; p<0.001 and 34.9±14.6 vs. 31.9±12.8 %; p<0.05, respectively). When compared to the apparently healthy control subjects, T2DM patients had significantly elevated PWVao (9.7±1.7 vs. 9.3±1.5 m/s; p<0.05, respectively), however the AIXao did not differ significantly. The ROC-curves of CAD and healthy control subjects explored cut-off values of 10.2 m/s for PWVao and 33.23 % for AIXao. Our data provide supporting evidence about impaired arterial stiffness parameters in CAD and T2DM. Our findings encourage the implementation of arterial stiffness measurements by oscillometric method in daily clinical routine., Z. Lenkey, M. Illyés, R. Böcskei, R. Husznai, Z. Sárszegi, Z. Meiszterics, F. T. Molnár, G. Hild, S. Szabados, A Cziráki, B. Gaszner., and Obsahuje bibliografii
Autoimmune endocrinopathies can be divided according to the presence of organ specific autoantibodies and according to the clinical manifestations into isolated autoimmune endocrinopathies, autoimmune polyglandular syndromes (APS) and polyglandular activation of autoimmunity (PAA). Many factors take part in the development of the autoimmune disease: predominantly a genetic predisposition, environmental etiologic causes and dysregulation in the microenvironment of the target organ. Until now it is not completely clear, if manifestations of the clinical disease depend primarily upon external factors and the degree of regulation mechanism disorder (e.g. in Th1/Th2 regulation) or upon the different genetic predisposition. In this work we compared the levels of Th1 and Th2 lymphocyte cytokines in peripheral blood in three groups of patients: group A of 30 patients with autoimmune thyroiditis, group B of 25 patients with PAA, and group C of 10 patients with APS type II. From group of Th1 cytokines IL-2 and IFN-Ύ were detected, whereas from group of Th2 cytokines IL-4 and IL-10 were determined by ELISA kit. We did not find any differences in the concentrations of IL-2, IFN-Ύ, IL-4 and IL-10 among the groups of patients with autoimmune endocrinopathies., P. Hrdá, I. Šterzl, P. Matucha., and Obsahuje bibliografii
The purpose of the present study was to examine whether the level of oxygen uptake (V.o2) at the onset of decrement-load exercise (DLE) is lower than that at the onset of constant-load exercise (CLE), since power output, which is the target of V.o2 response, is decreased in DLE. CLE and DLE were performed under the conditions of moderate and heavy exercise intensities. Before and after these main exercises, previous exercise and post exercise were performed at 20 watts. DEL was started at the same power output as that for CLE and power output was decreased at a rate of 15 watts per min. V.o2 in moderate CLE increased at a fast rate and showed a steady state, while V.o2 in moderate DLE increased and decreased linearly. V.o2 at the increasing phase in DLE was at the same level as that in moderate CLE. V.o2 immediately after moderate DLE was higher than that in the previous exercise by 98±77.5 ml/min. V.o2 in heavy CLE increased rapidly at first and then slowly increased, while V.o2 in heavy DLE increased rapidly, showing a temporal convexity change, and decreased linearly. V.o2 at the increasing phase of heavy DLE was the same level as that in heavy CLE. V.o2 immediately after heavy DLE was significantly higher than that in the previous exercise by 156±131.8 ml/min. Thus, despite the different modes of exercise, V.o2 at the increasing phase in DLE was at the same level as that in CLE due to the effect of the oxygen debt expressed by the higher level of V.o2 at the end of DLE than that in the previous exercise., T. Yano, H. Ogata, R. Matsuura, T. Arimitsu, T. Yunoki., and Obsahuje bibliografii a bibliografické odkazy
Hereditary hypertriglyceridemic (hHTG) rats are characterized by increased blood pressure and impaired endotheliumdependent relaxation of conduit arteries. The aim of this study was to investigate the effect of long-term (4 weeks) treatment of hHTG rats with three drugs which, according to their mechanism of action, may be able to modify the endothelial function: simvastatin (an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase), spironolactone (an antagonist of aldosterone receptors) and L-arginine (a precursor of nitric oxide formation). At the end of 4th week the systolic blood pressure in the control hHTG group was 148±2 mm Hg and in control normotensive Wistar group 117±3 mm Hg. L-arginine failed to reduce blood pressure, but simvastatin (118±1 mm Hg) and spironolactone (124±4 mm Hg) treatment significantly decreased the systolic blood pressure. In isolated phenylephrine-precontracted aortic rings from hHTG rats endothelium-dependent relaxation was diminished as compared to control Wistar rats. Of the three drugs used, only simvastatin improved acetylcholine-induced relaxation of the aorta. We conclude that both simvastatin and spironolactone reduced blood pressure but only simvastatin significantly improved endothelial dysfunction of aorta. Prominent increase in the expression of eNOS in large conduit arteries may be the pathophysiological mechanism underlying the protective effect of simvastatin in hHTG rats., J. Török, I. L'upták, J. Matúšková, O. Pecháňová, J. Zicha, J. Kuneš, F. Šimko., and Obsahuje bibliografii
The relative length of telomeres measured in peripheral blood leukocytes is a commonly used system marker for biological aging and can also be used as a biomarker of cardiovascular aging. However, to what extent the telomere length in peripheral leukocytes reflects telomere length in different organ tissues is still unclear. Therefore, we have measured relative telomere length (rTL) in twelve different human tissues (peripheral blood leukocytes, liver, kidney, heart, spleen, brain, skin, triceps, tongue mucosa, intercostal skeletal muscle, subcutaneous fat, and abdominal fat) from twelve cadavers (age range of 29 week of gestation to 88 years old). The highest rTL variability was observed in peripheral leukocytes, and the lowest variability was found in brain. We found a significant linear correlation between leukocyte rTL and both intercostal muscle (R=0.68, P<0.02) and liver rTL (R=0.60, P<0.05) only. High rTL variability was observed between different organs from one individual. Furthermore, we have shown that even slight DNA degradation (modeled by sonication of genomic DNA) leads to false rTL shortening. We conclude that the rTL in peripheral leukocytes is not strongly correlated with the rTL in different organs., D. Dlouha, J. Maluskova, I. Kralova Lesna, V. Lanska, J. A. Hubacek., and Obsahuje bibliografii
The objective of this study was to evaluate the influence of low-dose combined oral contraception (COC) on basal and stimulated (1 μg ACTH test) levels of serum and salivary cortisol (F), cortisone and on basal serum cortisol binding globulin (CBG), adrenocorticotropic hormone (ACTH), dehydroepiadrosterone (DHEA) and calculated free cortisol in healthy young women. Three-month administration of COC resulted in 1) significant increase of basal (454.0±125.0 to 860.9±179.7 nmol/l) and ACTH-stimulated serum cortisol in 30th min (652.3±60.5 to 1374.1±240.6 nmol/l); 2) no significant change of basal (15.4±7.3 to 18.9±8.5 nmol/l) and ACTH-stimulated salivary cortisol at the 30th min (32.4±8.8 to 32.9±9.0 nmol/l); 3) no significant change of basal serum cortisone (38,8±7.68 to 45.2±24.2 nmol/l) and ACTH-stimulated cortisone at the 30th (34.8±10.9 to 47.0±35.7 nmol/l); 4) significant increase of basal ACTH (17.2±9.0 to 38.2±29.4 ng/l), CBG (991.0±161.0 to 2332.0±428.0 nmol/l), and 5) no significant change of basal DHEA (24.6±15.7 to 22.6±11.7 μmol/l) and calculated basal value for free cortisol (22.8±14.9 to 19.2±6.9nmol/l). In conclusions, higher basal and ACTH-stimulated serum cortisol were found after three-month administration of COC, while basal and stimulated salivary cortisol were not significantly affected. Therefore, salivary cortisol can be used for assessment of adrenal function in women regularly using COC., K. Šimůnková, L. Stárka, M. Hill, L. Kříž, R. Hampl, K. Vondra., and Obsahuje bibliografii a bibliografické odkazy
This study investigated whether each part of the heart is evenly innervated by the left or right vagus and observed the mechanism of compensatory recovery after unilateral cervical vagotomy. HR, BP, LVSP and ±dp/dt max all decreased one week after left vagotomy, whereas only BP and -dp/dt max decreased one week after right vagotomy. We stern blot analyses revealed that the expression of M2 receptors in the left atrium and left ventricle was upregulated after subacute (1 week) left/right vagotomy. However, significantly more cholinesterase-positive nerves in LV and RV were seen one week after unilateral vagotomy compared to the sham-operated group. In addition, baroreflex sensitivity was increased after subacute right vagotomy. The decreasing effects of ACh (0.5 μ g/kg) on LVSP and ±dp/dt max (but not on HR and BP) were facilitated by subacute unilateral vagotomy. Our present experiments indicate that 1) the working myocardium is innervated bilaterally by the vagus, 2) ventricular contractility is influenced more by denervation of the left than the right vagus and 3) up-regulation of M2 muscarinic receptors in the left heart, increase of cholinergic nerves, and high baroreflex sensitivity could be involved in the mechanism of compensatory hemodynamic recovery via contralateral vagus overactivity, thereby amplifying contralateral vagal activity and decreasing cardiac contractility., L. N. Chen, W. J. Zang, X. J. Yu, J. Liu, D. L. Li, S. S. Kong, J. Lu, X. L. Xu., and Obsahuje bibliografii a bibliografické odkazy