The aim of this work was to investigate the effect of 10 weeks of lisinopril treatment to spontaneously hypertensive rats (SHRs) on day/night variations of blood pressure, heart rate and autonomic cardio-regulation parameters. Male SHR with surgically implanted radio-telemetry implant that provided direct measurements of arterial pressure and electrocardiogram wave were used. Animals were allocated to two groups (n=5 each). The first group was treated with lisinopril (20 mg/kg by gavage) daily for 10 weeks (treated group); whereas the second was gavaged daily with tap water (untreated group). Arterial blood pressure, ECG and other telemetry parameters were recorded at the start and at the end of 10-week treatment. Collected data were analyzed using specialized software and were statistically tested. In addition to the expected lowering of blood pressure, spectral analysis of R-R intervals revealed that lisinopril treatment for 10 weeks significantly caused 2-3 fold increase in heart rate variability (HRV) during both active and inactive periods. However, R-R interval durations demonstrated variable distribution patterns during those periods. The cause of observed distribution pattern of R-R intervals during active and inactive periods may be of significance to better understand HRV changes and warrants further investigations., S. Albarwani, S. Al-Siyabi, M. O. Tanira., and Obsahuje seznam literatury
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
Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are effective drugs in the treatment of hypercholesterolemia, however, their undesirable actions are not fully known. We investigated the effects of atorvastatin on the oxidative phosphorylation and membrane fluidity in liver mitochondria, and also on the coenzyme Q (CoQ) content in the mitochondria, liver tissue, and plasma of rats on a standard (C) and hypercholesterolemic (HCh) diet. Atorvastatin was administered at either low (10 mg⋅kg-1) or high dose (80 mg⋅kg-1) for four weeks. The high dose of the drug decreased the concentrations of total cholesterol and triacylglycerols in the plasma and liver of rats on a HCh diet. Administration of atorvastatin was associated with decreased oxygen uptake (state 3), and oxidative phosphorylation rate in the mitochondria of both C and HCh rats. Further, the drug influenced mitochondrial membrane fluidity and dose-dependently reduced concentrations of oxidized and reduced forms of CoQ in the mitochondria. Our findings point to an association between in vivo administration of atorvastatin and impaired bioenergetics in the liver mitochondria of rats, regardless of diet, in conjunction with simultaneous depletion of oxidized and reduced CoQ forms from the mitochondria. This fact may play a significant role in the development of statin-induced hepatopathy., O. Uličná ...[et al.]., and Obsahuje seznam literatury
The aim of this study was a comparison of risk stratification for death in patients after myocardial infarction (MI) and of risk stratification for malignant arrhythmias in patients with implantable cardioverter-defibrillator (ICD). The individual risk factors and more complex approaches were used, which take into account that a borderline between a risky and non-risky value of each predictor is not clear-cut (fuzzification of a critical value) and that individual risk factors have different weight (area under receiver operating curve - AUC or Sommers´ D - Dxy). The risk factors were baroreflex sensitivity, ejection fraction and the number of ventricular premature complexes/hour on Holter monitoring. Those factors were evaluated separately and they were involved into logit model and fuzzy models (Fuzzy, Fuzzy-AUC, and Fuzzy-Dxy). Two groups of patients were examined: a) 308 patients 7-21 days after MI (23 patients died within period of 24 month); b) 53 patients with left ventricular dysfunction examined before implantation of ICD (7 patients with malignant arrhythmia and electric discharge within 11 month after implantation). Our results obtained in MI patients demonstrated that the application of logit and fuzzy models was superior over the risk stratification based on algorithm where the decision making is dependent on one parameter. In patients with implanted defibrillator only logit method yielded statistically significant result, but its reliability was doubtful because all other tests were statistically insignificant. We recommend evaluating the data not only by tests based on logit model but also by tests based on fuzzy models., P. Honzík ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
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
Uric acid is involved in nitrogenous waste in animals, together with ammonia and urea. Uric acid has also antioxidant properties and is a surrogate marker of metabolic syndrome. We observed that the elevated plasma uric acid of high-fat fed mice was normalized by benzylamine treatment. Indeed, benzylamine is the reference substrate of semicarbazide-sensitive amine oxidase (SSAO), an enzyme highly expressed in fat depots and vessels, which generates ammonia when catalysing oxidative deamination. Ammonia interferes with uric acid metabolism/solubility. Our aim was therefore to investigate whether the lowering action of benzylamine on uric acid was related to an improvement of diabetic complications, or was connected with SSAO-dependent ammonia production. First, we observed that benzylamine administration lowered plasma uric acid in diabetic db/db mice while it did not modify uric acid levels in normoglycemic and lean mice. In parallel, benzylamine improved the glycemic control in diabetic but not in normoglycemic mice, while plasma urea remained unaltered. Then, uric acid plasma levels were measured in mice invalidated for AOC3 gene, encoding for SSAO. These mice were unable to oxidize benzylamine but were not diabetic and exhibited unaltered plasma uric levels. Therefore, activated or abolished ammonia production by SSAO was without influence on uric acid in the context of normoglycemia. Our observations confirm that plasma uric acid increases with diabetes and can be normalized when glucose tolerance is improved. They also show that uric acid, a multifunctional metabolite at the crossroads of nitrogen waste and of antioxidant defences, can be influenced by SSAO, in a manner apparently related to changes in glucose homeostasis., C. Carpéné ... [et al.]., and Obsahuje seznam literatury
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
Alterations in geometry and structure of coronary arteries have marked consequences on blood flow to the respective area. We evaluated long-term effect of losartan on blood pressure (BP), heart weight/body weight (HW/BW), geometry and structure of septal branch of coronary artery (RS) of young SHR and Wistar rats. Four-week-old Wistar rats and SHR were used. Losartan was administered (20 mg/kg/day) in drinking water by gavage for 5 weeks. BP was measured by plethysmographic method. Cardiovascular system was perfused with a fixative (120 mm Hg). RS was processed for electron microscopy. Wall thickness of intima + media (WT), inner diameter (ID), cross-sectional area of intima + media (CSA), volume dens ities (VD) of endothelial cells (EC), extracellular matrix (ECM) of intima, smooth muscle cells (SMC) and ECM of media were eval uated. BP of 4-week-old SHR did not differ from that of Wistar rats. BP, HW/BW, WT, CSA, WT/ID, CSAs of SMC, ECM of media were increased in 9-week- old SHR, whereas their VD and CSA of EC were decreased. Losartan administration decreased BP and HW/BW in both groups. Geometry of RS was affected only in SHR (reduction of WT, CSA, WT/ID and increased of ID, circumferential tension, VD and CSA of EC). Losartan administration reduced BP and myocardial mass in both groups and beneficially affected geometry and structure of coronary artery in SHR., R. Koprdová, M. Cebová, F. Kristek., and Obsahuje seznam literatury
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