The role of brain derived nitric oxide in the physiology and behavior remains disputable. One of the reasons of the controversies might be systemic side effects of nitric oxide synthase inhibitors. Therefore, under nNOS inhibition by 7- nitroindazole (7-NI) we carried out recordings of blood gasses, blood pressure and spontaneous EEG in conscious adult rats. Locomotion and spontaneous behavior were assessed in an open field. In addition skilled walking and limb coordination were evaluated using a ladder rung walking test. The blood gas analysis revealed a significant increase in pCO2 180 min and 240 min after the application of 7-NI. The power and entropy decreased simultaneously with a shift of the mean frequency of the spontaneous EEG toward slow oscillations after 7-NI treatment. The thresholds of evoked potentials underwent a significant drop and a trend towards a slight increase in the I-O curve slope was observed. 7-NI significantly suppressed open field behavior expressed as distance moved, exploratory rearing and grooming. As for the ladder rung walking test the 7-NI treated animals had more errors in foot placement indicating impairment in limb coordination. Therefore our findings suggest that 7-NI increased cortical excitability and altered some physiological and behavioral parameters., C. Boržíčková, A. Mikulecká, J. Otáhal., and Obsahuje bibliografii
Statins are powerful lipid-lowering drugs, widely used in patients with hyperlipidemia and coronary artery disease. It was found, however, that statins appear to have a pleiotropic effect beyond their lipid-lowering ability. They exert anti-inflammatory, antithrombotic and antioxidant effects, increase nitric oxide production and improve endothelial dysfunction. The aim of our study was to examine the effect of chronic and acute treatment with simvastatin on the contractile function of the isolated perfused rat heart after ischemia/reperfusion injury. Contractile function was measured on isolated rat hearts, perfused according to Langendorff under constant pressure. The hearts were subjected to 20 min of global ischemia, followed by 40 min of reperfusion. To investigate the acute effect, simvastatin at a concentration of 10 μmol/l was added to the perfusion solution during reperfusion. In chronic experiments the rats were fed simvastatin at a concentration of 10 mg/kg for two weeks before the measurement of the contractile function. Acute simvastatin administration significantly increased reparation of the peak of pressure development [(+dP/dt)max] (52.9±8.2 %) after global ischemia, as compared with the control group (28.8±5.2 %). Similar differences were also observed in the time course of the recovery of [(+dP/dt)max]. Chronic simvastatin was without any protective effect. Our results reveal that the acute administration of simvastatin during reperfusion, unlike the chronic treatment, significantly reduced contractile dysfunction induced by ischemia/reperfusion injury. This supports the idea of possible cardioprotective effect of statin administration in the first-line therapy of the acute coronary syndrome., O. Szárszoi, J. Malý, P. Ošťádal, I. Netuka, J. Bešík, F. Kolář, B. Ošťádal., and Obsahuje bibliografii a bibliografické odkazy
Animal models of neuropsychiatric disorders are current topics in behavioral neuroscience. Application of non-competitive antagonists of NMDA receptors (such as MK-801) was proposed as a model of schizophrenia, as it leads to specific behavioral alterations, which are partly analogous to human psychotic symptoms. This study examined an animal model of schizophrenia induced by a systemic application of MK-801 (0.15 and 0.20 mg/kg) into rats tested in the active allothetic place avoidance (AAPA) task. Previous studies suggested that MK-801 may interact in vivo with other neurotransmitter systems, including noradrenergic system. Our experiments therefore evaluated the hypothesis that both locomotor stimulation and deficit in avoidance behavior in AAPA task induced by this drug would be reversible by application of alpha1-adrenergic antagonist prazosin (1 and 2 mg/kg). The results showed that both doses of prazosin partia lly reversed hyperlocomotion induced by higher doses of MK-801 and an avoidance deficit measured as number of entrances into the shock sector. Interestingly, no effect of prazosin on the MK-801-induced decrease of maximum time between two entrances (another measure of cognitive performance) was observed. These results support previous data showing that prazosin can compensate for the hyperlocomotion induced by MK-801 and newly show that this partial reduction sustains even in the forced locomotor conditions, which are involved in the AAPA task. The study also shows that certain parameters of avoidance efficiency may be closely related to locomotor activity, whereas other measures of cognition may more selectively reflect cognitive changes., A. Stuchlík, T. Petrásek, K. Valeš., and Obsahuje seznam literatury
Stellate ganglion blockade (SGB) with a local anesthetic increases muscle sympathetic nerve activity in the tibial nerve in humans. However, whether this sympathetic excitation in the tibial nerve is due to a sympathetic blockade in the neck itself, or due to infiltration of a local anesthetic to adjacent nerves including the vagus nerve remains unknown. To rule out one mechanism, we examined the effects of cervical sympathetic trunk transection on renal sympathetic nerve activity (RSNA) in anesthetized rats. Seven rats were anesthetized with intraperitoneal urethane. RSNA together with arterial blood pressure and heart rate were recorded for 15 min before and 30 min after left cervical sympathetic trunk transection. The baroreceptor unloading RSNA obtained by decreasing arterial blood pressure with administration of sodium nitroprusside was also measured. Left cervical sympathetic trunk transection did not have any significant effects on RSNA, baroreceptor unloading RSNA, arterial blood pressure, and heart rate. These data suggest that there was no compensatory increase in RSNA when cervical sympathetic trunk was transected and that the increase in sympathetic nerve activity in the tibial nerve during SGB in humans may result from infiltration of a local anesthetic to adjacent nerves rather than a sympathetic blockade in the neck itself., T. Ikeda ... [et al.]., and Obsahuje seznam literatury
It is documented that in chronic hypertensive state there is an increased vasodepressor response to calcium channel antagonists such as the dihydropyridine derivate nifedipine. This effect is generally proportional to initial blood pressure as was demonstrated in several models of experimental hypertension. In the present study we investigated the effect of chronic nifedipine treatment on the development of cardiovascular system in young spontaneously hypertensive rats (SHR) in order to evaluate whether it could prevent the abnormalities leading to hypertensive state. Four- and eight-week-old rats were treated with nifedipine (50 mg/kg/day) for 4 weeks. Blood pressure of nifedipine-treated SHR remained at the initial level in contrast to their untreated controls where it continued to increase. In both age groups, chronic nifedipine administration reduced neurogenic contractions of isolated superior mesenteric artery, but did not significantly affect the dose-response curve to exogenous noradrenaline in 8-week-old rats. In contrast, maximum response to noradrenaline was significantly attenuated in mesenteric artery of 12-week-old nifedipine-treated SHR. We can presume that the antihypertensive effect of nifedipine is similar in both stages of spontaneous hypertension development, but the mechanisms involved might be different. It seems that chronic reduction of calcium influx during the rapid phase of pathological blood pressure increase in SHR may eliminate the effect of enhanced sympathetic tone, which may have unfavorable consequences on cardiovascular structure and function., A. Zemančíková, J. Török., and Obsahuje seznam literatury
We examined the effect of ethanol on single potassium channels derived from plasma membranes of bovine tracheal smooth muscles. The observed potassium channels had a conductance of 296±31 pS (mean ± S.D.) in symmetrical 250 mmol/l KCl solutions, and exhibited a voltage- and Ca2+-dependence similar to BKCa channels. Ethanol at 50, 100 and 200 mM concentrations increased the probability of open potassium channels to 112±5, 127±7 and 121±13% (mean ± S.E.M.), respectively. It is suggested that increased activity of the BKCa channels by ethanol hyperpolarizes the plasma membrane and thus may contribute to relaxation of tracheal smooth muscle., V. Komínková, M. Magová, A. Mojžišová, Ľ. Máleková, K. Ondriaš., and Obsahuje bibliografii
Intrauterine and perinatal life are critical periods for programming of cardiometabolic diseases. However, their relative role remains controversial. We aimed to assess, at weaning, sexdependent alterations induced by fetal or postnatal nutritional interventions on key organs for metabolic and cardiovascular control. Fetal undernutrition was induced by dam food restriction (50 % from mid-gestation to delivery) returning to ad libitum throughout lactation (Maternal Undernutrition, MUN, 12 pups/litter). Postnatal overfeeding (POF) was induced by litter size reduction from normally fed dams (4 pups/litter). Compared to control, female and male MUN offspring exhibited: 1) low birth weight and accelerated growth, reaching similar weight and tibial length by weaning, 2) increased glycemia, liver and white fat weights; 3) increased ventricular weight and tendency to reduced kidney weight (males only). Female and male POF offspring showed: 1) accelerated growth; 2) increased glycemia, liver and white fat weights; 3) unchanged heart and kidney weights. In conclusion, postnatal accelerated growth, with or without fetal undernutrition, induces early alterations relevant for metabolic disease programming, while fetal undernutrition is required for heart abnormalities. The progression of cardiac alterations and their role on hypertension development needs to be evaluated. The similarities between sexes in pre-pubertal rats suggest a role of sex-hormones in female protection against programming., D. Muñon-Valverde, P. Rodríguez-Rodríguez, P. Y. Gutierrez-Arzapalo, A. L. López de Pablo, M. Carmen González, R. López-Giménez, B. Somoza, S. M. Arribas., and Obsahuje bibliografii
Activation of GABAB receptors leads to longer inhibitory postsynaptic potentials than activation of GABAA receptors. Therefore GABAB receptors may be a target for anticonvulsant therapy. The present study examined possible effects of GABAB receptor agonist SKF97541 on cortical and hippocampal epileptic afterdischarges (ADs). Epileptic ADs elicited by electrical stimulation of sensorimotor cortex or dorsal hippocampus were studied in adult male Wistar rats. Stimulation series were applied 6 times with 10- or 20-min interval. Either interval was efficient for reliable elicitation of cortical ADs but stimulation at 10-min intervals did not reliably elicit hippocampal ADs, many stimulations were without effect. SKF97541 in dose 1 mg/kg significantly prolonged cortical ADs. Duration of hippocampal ADs was not significantly changed by either dose of SKF97541 in spite of a marked myorelaxant effect of the higher dose. Our present data demonstrated that neither cortical nor hippocampal ADs in adult rats were suppressed by GABAB receptor agonist SKF97541. Proconvulsant effect on cortical ADs indicates a different role in these two brain structures. In addition, duration of refractory period for electrically-induced ADs in these two structures in adult rats is different., P. Fábera, P. Mares., and Obsahuje bibliografii
Hindlimb unweighting (HU) leads to capillary regression in skeletal muscle. However, the molecular mechanism(s) remains to be elucidated. To gain insight into the regulation of this process, we investigated gene expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), angiopoietin, and their receptors in the atrophied muscle induced by HU. The hindlimbs of mice were unweighted by tail-suspension and then the gastrocnemius muscles were isolated after 10 days. To assess the capillary distribution, the capillary endothelium in frozen transverse sections was identified by staining for alkaline phosphatase. The mRNA levels were analyzed using a real-time reverse transcription-polymerase chain reaction. After 10 days of HU, the number of capillaries around a muscle fiber was significantly decreased by 19.5 %, suggesting that capillary regression appears to occur. The expression of HIF-1α was significantly down-regulated after 10 days of HU. The expression of VEGF remained unchanged, whereas those of Flt-1, KDR/Flk-1, and neuropilin-1 were significantly down-regulated, suggesting that VEGF signaling through these receptors would be attenuated. The expression of angiopoietin-1, and -2, as well as their receptor, Tie-2 were also significantly down-regulated, suggesting that angiopoietin-1 signaling through Tie-2 would be attenuated. These findings suggest that alterations in expression of VEGF, angiopoietins, and their receptors may be associated with capillary regression after HU., A. Wagatsuma., and Obsahuje biblografii a bibliografické odkazy
Vasodilator prostaglandins (PGE2, PGI2) play an important role in the regulation of renal blood flow. Hence, inhibition of their production with nonsteroidal anti-inflammatory drugs increases renal vascular resistance and exerts adverse renal effects. It has been reported that besides endothelium-derived prostaglandin products, nitric oxide (NO) may be mainly involved in regulation of renal functions. The aim of our study was to evaluate the effect of cyclooxygenase inhibition with indomethacin and endothelium removal on vascular responses of the renal artery as a model vessel. Isolated segments of rabbit renal arteries were perfused at constant flow. Indomethacin administration (10-5mol.l-1) significantly increased the responses to single doses (0.1, 1, 10 m g) of noradrenaline (NA) as compared with the controls. In indomethacin-pretreated vessels, subsequent deendothelisation by air bubbles enhanced the constrictor responses to NA. In reversed order, when deendothelisation was followed by indomethacin administration, the responses to NA were similar in character. A comparison of renal artery responses to NA in both experimental situations did not reveal any significant differences. It can be supposed that endothelial and non-endothelial factors may be involved in local regulation of renal vascular tone., V. Kristová, M. Kriška, R. Vojtko, A. Kurtanský., and Obsahuje bibliografii