We investigated the effect of pertussis toxin (PTX) on hypotensive response induced by acetylcholine (ACh) and bradykinin (BK) and on noradrenaline (NA)-induced pressor response in spontaneously hypertensive rats (SHR). Fifteen-week-old Wistar rats and age-matched SHR were used. Half of SHR received PTX (10 μg/kg/i.v.) and the experiments were performed 48 h later. After the anesthesia the right carotid artery was cannulated in order to record blood pressure (BP). The hypotensive response to ACh was enhanced in SHR compared to Wistar rats. After pretreatment of SHR with PTX the hypotensive response to ACh was reduced compared to untreated SHR and it was also diminished in comparison to Wistar rats. Similarly, the hypotensive response to BK was also decreased after PTX pretreatment. The pressor response to NA was increased in SHR compared to Wistar rats. NA-induced pressor response was considerably decreased after PTX pretreatment compared to untreated SHR. In conclusion, the enhancement of hypotensive and pressor responses in SHR was abolished after PTX pretreatment. Our results suggested that the activation of PTX-sensitive inhibitory Gi proteins is involved in the regulation of integrated vasoactive responses in SHR and PTX pretreatment could be effectively used for modification of BP regulation in this type of experimental hypertension., S. Čačányiová, F. Kristek, J. Kuneš, J. Zicha., and Obsahuje bibliografii a bibliografické odkazy
The functional aversive stimulus properties of several IP doses of (±)-amphetamine (1.25-10 mg.kg-1), 2-phenylethylamine (PEA, 2.5-10 mg.kg-1, following inhibition of monoamine oxidase with pargyline 50 mg.kg-1) and phenylethanolamine (6.25-50 mg.kg 1) were measured with the conditioned taste aversion (CTA) paradigm. A two bottle choice procedure was used, water vs. 0.1 % saccharin with one conditioning trial and three retention trials. (±)-Amphetamine and phenylethanolamine induced a significant conditioned taste aversion but PEA did not. (±)-Amphetamine and PEA increased spontaneous locomotor activity but phenylethanolamine had no effects on this measure. Measurement of whole brain levels of these drugs revealed that the peak brain elevation of PEA occurred at approximately 10 min whereas the peak elevations of (±)-amphetamine and phenylethanolamine occurred at approximately 20 min. The present failure of PEA to elicit conditioned taste aversion learning is consistent with previous reports for this compound. The differential functional aversive stimulus effects of these three compounds are surprising since they exhibit similar discriminative stimulus properties and both (±)-amphetamine and PEA are self-administered by laboratory animals. The present data suggest that time to maximal brain concentrations following peripheral injection may be a determinant of the aversive stimulus properties of PEA derivatives., A.J. Greenshaw, S. Turkish, B.A. Davis., and Obsahuje bibliografii
Taste is important for food intake. The fetus first experiences taste through amniotic fluid, and later via mother’s milk. Early human experience with taste has a key importance for later acceptance of food. Dietary behavior is determined by the interaction of many different factors. The development of the olfactory and taste receptors begins at 7-8 weeks of gestation. An early sensitive period probably exists when flavor preference is established. Sweet taste is preferred in early childhood; this is the reason why children are at increased risk of over-consuming saccharides. Gustatory sensitivity declines with age. The threshold for the perception of each basic taste differs, and is established genetically. In this review, we summarize published data on taste preferences and its development and changes during life., Š. Podzimek, M. Dušková, Z. Broukal, B. Rácz, L. Stárka, J. Dušková., and Obsahuje bibliografii
Previous studies have suggested that the Notch signaling pathway plays a very important role in the proliferation and differentiation of pulmonary microvascular endothelial cells (PMVECs). Therefore, we aimed to investigate the expression level of Notch-related signaling molecules in PMVECs in bleomycin (BLM)-induced rat pulmonary fibrosis. Immunohistochemistry, immunofluorescence, Western blotting, and real-time PCR were used to analyze the differences in protein and mRNA expression levels of Notch-related signaling molecules, i.e. Notch1, Jagged1, Delta-like ligand 4 (Dll4), and hairy and enhancer of split homolog 1 (Hes1), between a control group treated with intratracheal instillation of saline and a study group treated with intratracheal instillation of BLM solution. Expression levels of the receptor Notch1 and one of its ligands, Jagged1, were upregulated, while the expression levels of the ligand Dll4 and the target molecule of the Notch signaling pathway, Hes1, were downregulated. The differences in protein and mRNA expression levels between the control and study groups were significant (p<0.001). The Jagged1/Notch1 signaling pathway is activated in the pathogenesis of BLM-induced rat pulmonary fibrosis, while the Dll4/Notch1 signaling pathway is inhibited, which inhibits the suppressive effect of Dll4/Notch1 signaling on PMVEC overproliferation, further causing PMVEC dysfunction in cell sprouting and maturation as well as abnormal differentiation of the cell phenotype. Conversely, the downexpression of Hes1 indicates that the Jagged1/Notch1 signaling pathway could be a non-canonical Notch signaling pathway independent of Hes1 activation, which differs from the canonical Dll4/Notch1 signaling pathway., Q. Yin, W. Wang, G. Cui, H. Nan, L. Yan, W. Zhang, S. Zhang, J. Wei., and Obsahuje bibliografii
Doctor David J. Webb MD, DSc, FRCP, FRSE, FMedSci, a clinical pharmacologist specialising in the management of cardiovascular disease, is the recipient of The Fourth Tomoh Masaki Award , a bi-annual prize presented on the occasion of the International Conferences on Endothelin to scientists for outstanding contributions and achievements in the field of endothelin research. The Fourth Tomoh Masaki Award was presented to Doctor Webb at the Fifteenth International Conference on Endothelin which was held at Duo Hotel, Prague, Czech Republic, in October 2017. The award was granted to Dr. Webb during the Award Ceremony in Troja Chateau “In Recognition of his Outstanding Contributions to Science and Endothelin Research in Particular”. This article summarises the career and the scientific achievements of David J. Webb viewed by his former student Dr. Neeraj Dhaun, known to everybody as ‘Bean’., N. Dhaun., and Seznam literatury
The glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide is an incretin hormone mimetic used in the treatment of diabetes. However, the effects of liraglutide on pulmonary hypertension (PH) and pulmonary endothelin (ET) system are unknown. Eight-week-old C57BL6/J mice were injected liraglutide or vehicle for 5 weeks. One week after injection, the mice were exposed to either room air (normoxia) or chronic hypoxia (10 % O2) for 4 weeks. The right ventricular systolic pressure (RVSP) was significantly higher in hypoxia + vehicle group than in normoxia + vehicle group. ET-1 mRNA expression in the lungs was comparable among all the groups. ETB mRNA and protein expression in the lungs was significantly lower in hypoxia + vehicle group than in normoxia + vehicle group. The above changes were normalized by liraglutide treatment. The expression of phospho-eNOS and phospho-AMPK proteins in the lungs was significantly higher in hypoxia + liraglutide group than in normoxia + vehicle group. We demonstrated for the first time that liraglutide effectively improved RVSP and RV hypertrophy in hypoxia-induced PH mice by activating eNOS through normalization of impaired ETB pathway and augmentation of AMPK pathway. Therefore, GLP-1R agonists can be promising therapeutic agents for PH., J. Honda, T. Kimura, S. Sakai, H. Maruyama, K. Tajiri, N. Murakoshi, S. Homma, T. Miyauchi, K. Aonuma., and Seznam literatury
It is well known that the training level of a muscle belongs to the parameters that affect the H-reflex response amplitude. The aim of this study was to investigate the effects of training type on H- and T-reflex response parameters. For this purpose, 20 long-distance athletes (group I, test group), 18 short-distance athletes (group II, test group) and 20 non-trained subjects (group III, control group) were involved in this study in which the H- and T-reflex amplitude and latency values were measured. The H-reflex amplitude and latency values found in groups I, II and III were 3.64±0.28 mV and 26.88±1.45 ms, 3.17±0.26 mV and 26.19±1.89 ms, and 6.07±0.34 mV and 26.77±1.32 ms, respectively. The T-reflex amplitude and latency values of the groups I, II and III were 3.30±0.18 mV and 32.01±1.02 ms, 3.11±0.20 mV and 31.47±1.16 ms, 4.24±0.21 mV and 31.47±1.16 ms, respectively. There was no statistically significant difference between the groups with respect to latencies of H- and T-reflexes (p>0.05). In both test groups, the amplitudes of the H-reflex and T-reflex were significantly smaller than the control group (p<0.05). The results of this study suggest that training of muscles affect the H- and T-reflex response parameters., R. Ozmerdivenli, S. Bulut, T. Urat, A. Ayar., and Obsahuje bibliografii
Cytokines are widely known mediators of inflammation accompanying many neurodegenerative disorders including normal pressure hydrocephalus (NPH). NPH is caused by impaired cerebrospinal fluid (CSF) reabsorption and treated by surgical shunt insertion. The diagnostics is still complicated and the shunt effect is not durable; after several years, dementia may develop. In the clinical practice, biomarkers support the diagnostics as well as the further time course of many neurodegenerative diseases. Until recently, no reliable biomarker for NPH was evaluated. The attempt of this review was to make a survey concerning cytokines as possible NPH markers. Among all reviewed cytokines, the most promising are CSF IL-10 and IL-33, enabling to follow-up the disease progression and monitoring the effectiveness of the shunt insertion., L. Sosvorova, M. Mohapl, J. Vcelak, M. Hill, J. Vitku, R. Hampl., and Obsahuje bibliografii
Previous studies of physiological responses to music and noise showed the effect on the autonomic nervous system. The heart rate variability (HRV) has been used to assess the activation of the sympathetic and the parasympathetic nervous systems. The present study was aimed to examine HRV with exposure to four sine-wave pure tones (20 Hz, 50 Hz, 2 kHz and 15 kHz) in an environment where the sound intensity exceeded level 65 dB (A-weighted). The participants (20 adolescent girls) were lying in supine position during exposure protocol divided into 6 periods, the first time with generated sounds and the second time without sounds. In the protocol without sound exposure, the low frequency band of the HRV spectrum was increased compared to the basal state before examination (period_1: 6.05±0.29 ms2 compared to period_5: 6.56±0.20 ms2, p<0.05). The significant increase of root Mean Square of the Successive Differences (rMSSD, period_1: 4.09±0.16 s compared to period_6: 4.33±0.12 s, p<0.05) and prolongation of R to R peak (RR) interval (period_1: 889±30 ms compared to period_5: 973±30 ms, p<0.001) were observed in the protocol without sound exposure comparing to the protocol with sound exposure where only bradycardia was observed. Contrary to rather polemical data in literature our pilot study suggests that sounds (under given frequencies) have no impact on the heart rate variability and cardiac autonomic regulation., M. Veternik, I. Tonhajzerova, J. Misek, V. Jakusova, H. Hudeckova, J. Jakus., and Obsahuje bibliografii