To investigate lisinopril effect on the contribution of nitric oxide (NO) and KCa channels to acetylcholine (ACh)-induced relaxation in isolated mesenteric arteries of spontaneously hypertensive rats (SHRs). Third branch mesenteric arteries isolated from lisinopril treated SHR rats (20 mg/kg/day for ten weeks, SHR-T) or untreated (SHR-UT) or normotensi ve WKY rats were mounted on tension myograph and ACh concentration-response curves were obtained. Westernblotting of eNOS and K Ca channels was performed. ACh-induced relaxations were similar in all groups while L-NMMA and indomethacin caused significant rightward shift only in SHR-T group. Apamin and TRAM-34 (SKCa and IKCa channels blockers, respectively) significantly attenuated ACh-induced maximal relaxation by similar magnitude in vessels from all three groups. In the presence of L-NMMA, indomethacin, apamin and TRAM-34 further attenuated ACh-induced relaxation only in SHR-T. Furthermore, lisinopril treatment increased expression of eNOS, SKCa and BKCa proteins. Lisinopril treatment increased expression of eNOS, SKCa , BKCa channel proteins and increased the contribution of NO to ACh-mediated relaxation. This increased role of NO was apparent only when EDHF component was blocked by inhibiting SKCa and IKCa channels. Such may suggest that in mesenteric arteries, non-EDHF component functions act as a reserve system to provide compensatory vasodilatation if (and when) hyperpolarization that is mediated by SKCa and IKCa channels is reduced, S. Albarwani, S. Al-Siyabi, I. Al-Husseini, A. Al-Ismail, I. Al-Lawati, I. Al-Bahrani, M. O. Tanira., and Obsahuje bibliografii
Distribution of LiCl/pilocarpine status epilepticus-induced neuronal damage was studied in the piriform cortex and in adjoining structures in 12-day-old, 25-day-old and adult rats. No distinct structural and neuronal alterations were detected in the basal telencephalon in 12-day-old rats surviving status epilepticus (SE) for one week or two months. In 25-day-old rats a decrease in Nissl staining was evident. There was also cell loss and gliosis in the caudal 2/3 of the piriform cortex, in the superficial amygdaloid nuclei, in the dorsal and ventral endopiriform nucleus and in the rostrolateral part of the entorhinal cortical area. In adult animals, the topography of neuropathological changes in the basal telencephalon was comparable to those in 25-day-old rats. The damage in the caudal 2/3 or caudal half of the piriform cortex in adult rats with survival times one week or two months was characterized by a marked loss of neurons and striking glial infiltration. The thickness of the piriform cortex and superficial amygdaloid nuclei was significantly reduced. In 25-day-old and in adult animals the sublayer IIb and layer III of the piriform cortex was more affected, while sublayer IIa was less damaged. Parvalbumin (PV) immunocytochemistry revealed a significant decrease in the number of PV-immunoreactive neurons in the rostral piriform cortex and in the dorsal claustrum in animals surviving for two months., R. Druga, H. Kubová, L. Suchomelová, R. Haugvicová., and Obsahuje bibliografii
Uni-quantal endplate currents (EPCs) were recorded extracellularly at the frog neuromuscular synapse and their latency dispersions expressed as P90 were estimated in the presence of acetylcholine. Stimulation-evoked EPCs with long release latencies increased in number when acetylcholine was applied. P90, which is designated as the interval between the minimal synaptic delay and the time at which 90 % of all measured uni-quantal EPCs had occurred, was significantly and reversibly increased by 66% from 0.51 ms to 0.85 ms in the presence of 5x10-4 M acetylcholine. This indicates that the evoked release pattern is less synchronous and the increased asynchrony leads to a substantial drop (by 28%) in the amplitude of reconstructed multi-quantal currents., D. Samigullin, E. A. Bukharaeva, E. Nikolsky, S. Adámek, F. Vyskočil., and Obsahuje bibliografii
NG-nitro-D-arginine-methyl ester (D-NAME) is considered to be an inactive enantiomer of L-NAME and is generally used as the negative control for NO synthase inhibition with L-NAME. With the aim to compare the effects of 4-week L-NAME and D-NAME treatments on hemodynamic and cardiovascular structural parameters, four groups of male Wistar rats were investigated: the controls and groups administered 40 and 20 mg/kg/day of L-NAME and 40 mg/kg/day of D-NAME. At the end of the experiment, myocardial NO synthase activity decreased by 42, 24 and 25 %; aortic NO synthase activity decreased by 35, 15 and 13 % vs. controls in the L-NAME 40, L-NAME 20 and D-NAME 40 groups, respectively. The DNA concentrations in the myocardium and the aorta increased significantly after L-NAME and D-NAME treatments. The inhibition of NO synthase was accompanied by a significant elevation in systolic blood pressure in all three groups. The LVW/BW ratio increased by 27, 14 and 13 % vs. controls in the L-NAME 40, L-NAME 20 and D-NAME 40 groups, respectively. The aortic wall mass, measured as the crossectional area, increased by 45, 17 and 25 % vs. controls in the L-NAME 40, L-NAME 20 and D-NAME 40 groups, respectively. Myocardial fibrosis represented 0.94 % in the controls, but 7.96, 4.70 and 5.25 % in L-NAME 40, L-NAME 20 and D-NAME 40 groups, respectively. It is concluded that D-NAME, although less affective than L-NAME, inhibits NO synthase activity resulting in hemodynamic and structural changes in the cardiovascular system similar to the changes induced by half the dose of L-NAME. Thus, the consideration of D-NAME as an inactive enantiomer and its use as the negative control needs to be reevaluated., P. Babál, O. Pecháňová, I. Bernátová., and Obsahuje bibliografii
We studied the effects of long-term administration of molsidomine and pentaerythrityl tetranitrate (PETN) on the cardiovascular system of spontaneously hypertensive rats (SHR). One control and three experimental groups of 10-week-old animals were used: 1) control Wistar rats, 2) SHR, 3) SHR treated with molsidomine in tap water (100 mg/kg/day, by gavage), and 4) SHR treated with PETN in tap water (200 mg/kg/day, by gavage). After six weeks, the content of cGMP in platelets and NO synthase (NOS) activity in aortas were evaluated in the experimental groups. For morphological evaluation the rats were perfused at 120 mm Hg with a glutaraldehyde fixative and the arteries were processed for electron microscopy. Blood pressure and heart weight/body weight ratio (HW/BW) were increased in all experimental groups with respect to the controls. HW/BW was lower in the molsidomine group in comparison to both SHR and PETN-treated group. The platelet content of cGMP was increased and the activity of NOS in the aortas was decreased in the molsidomine and PETN-treated groups. Wall thickness and cross-sectional area of thoracic aorta, carotid artery and coronary artery were increased similarly in all experimental groups compared to the controls, but there were no differences among the experimental groups. We summarize that long-term administration of exogenous NO donors did not improve pathological changes of the cardiovascular system in SHR., F. Kristek, V. Fáberová, I. Varga., and Obsahuje bibliografii
To determine whether the exposure to long term enriched environment (EE) would result in a continuous improvement of neurological recovery and ameliora te the loss of brain tissue after traumatic brain injury (TBI) vs. standard housing (SH). Male Sprague-Dawley rats (300-350 g, n=28) underwent lateral fluid percussion brain injury or SHAM operation. One TBI group was held under complex EE for 90 days, the other under SH. Neuromotor and sensorimotor dysfunction and recovery were assessed after injury and at days 7, 15, and 90 via Composite Neuroscore (NS), RotaRod test, and Barnes Circular Maze (BCM). Cortical tissue loss was assessed using serial brain sections. After day 7 EE animals showed similar latencies and errors as SHAM in the BCM. SH animals performed notably worse with differences still significant on day 90 (p<0.001). RotaRod test and NS revealed superior results for EE animals after day 7. The mean cortical volume was significantly higher in EE vs. SH animals (p=0.003). In summary, EE animals after lateral fluid percussion (LFP) brain injury performed sign ificantly better than SH animals after 90 days of recovery. The window of opportunity may be wide and also lends further credibility to the importance of long term interventions in patients suffering from TBI., M. Maegele, M. Braun, A. Wafaisade, N. Schäfer, M. Lippert-Gruener, C. Kreipke, J. Rafols, U. Schäfer, D. N. Angelov, E. K. Stuermer., and Obsahuje bibliografii
Little is known about the effect of chronic angiotensin-converting enzyme inhibition on the catecholamine levels in fowls. In this study, we investigated the effects of chronic lisinopri1 dihydrate (Ld) application on the plasma levels of adrenaline and noradrenaline and on the blood pressure. Lisinopril was given in different concentrations (25, 75 and 250 mg/l drinking water) to the white Leghorn chickens for 9 weeks, while the control group drank tap water only. Twenty-eight hours after the last lisinopril application, arterial blood pressure (BP), plasma adrenaline and noradrenaline levels, plasma renin (PRA) and plasma angiotensin-converting enzyme (ACE) activities were determined. In all concentrations, lisinopril significantly increased PRA and decreased ACE activities. Arterial BP was decreased only in the group receiving high lisinopril concentration (Controls 119±10.27, Ld3 98±5.4 mm Hg). However, the lower lisinopril concentrations did not alter arterial BP compared to the control group. Plasma noradrenaline levels were decreased in a concentration-dependent manner (47-58 %), but plasma adrenaline levels remained unchanged. The heart weight/body weight ratio was not changed in any of the lisinopril-treated groups. The persistent decrease in the blood pressure after lisinopril treatment was not directly related to a decrease of plasma ACE activity or plasma noradrenaline levels. Its mechanism still remains to be elucidated., H. S. Ozdemir, H. E. Aksulu, F. Karataş, B. Ustündag, I. Bingöl., and Obsahuje bibliografii
Advanced atherosclerotic changes can often resist even to very aggressive treatment. Although basic mechanisms of its origin and development are known, some important steps in this process are still waiting for more detailed explanation. Therefore, in addition to already proved aggressive lowering of LDL cholesterol, appropriate timing of atherosclerosis treatment is of the essence. Revealing different stages of atherosclerotic process, less or more sensitive to treatment is of primary importance; however, its detection is complicated by several facts including not exactly identifiable periods of quiescence and progression of atherosclerotic process. One of populations, study of which could add valuable information regarding this problem , are women in menop ausal transition. Previously unsuccessful therapy with hormone replacement therapy is restudied with focus on the time of/after menopause. Now, it is supposed to be favorable in women soon, approximately less than 8 years, after menopause. In addition, the same principle - optimal timing of the intervention of traditional cardiovascular risk factors, especially lipids, could be also of importance. Therefore, menopausal transition could be optimal period for the intervention in women at risk. However, this a pproach is to be proved by evidence from controlled prospective studies focused on lifestyle and/or pharmacological intervention., J. Piťha., and Obsahuje bibliografii
Domoic acid (DA) is a potent marine neurotoxine present in seafood. Intoxication by DA causes gastrointestinal symptoms like vomiting and diarrhoea and also the so-called amnesic shellfish poisoning (inflicting memory impairment and seizures). Since exposure to non-convulsive doses is relevant to the human health, we investigated the effect of low dose DA administration in adult Wistar rats. Rats were administered with DA at the dose 1.0 mg/kg and their behavior was monitored for one hour in three sessions. The first session started immediately after DA administration. The second and third session started one and two weeks later. After the third session, the histochemical analysis of the hippocampi of the animals was conducted (Fluoro-Jade B, bis-benzimide). DA increased time spent by locomotion and distance travelled in the second half of the first session and this effect was pronounced during the second and third session. Exploratory rearing was decreased by DA administration in the first half of the first session. DA influenced the grooming in biphasic manner (decrease followed by an increase of time spent by grooming). This biphasic trend was observed even two weeks after the DA administration. Histochemistry of DA treated rats did not confirm the presence of apoptotic bodies, Fluoro-Jade B positive cells were not found neither in CA1 nor CA3 area of the hippocampi. Our study revealed that a low dose of DA affect short and long-term the spontaneous behavior of rats without inducing neuronal damage., M. Schwarz, K. Jandová, I. Struk, D. Marešová, J. Pokorný, V. Riljak., and Obsahuje bibliografii