The production of the pineal hormone melatonin is synchronized with day-night cycle via multisynaptic pathway including suprachiasmatic nucleus linking several physiological functions to diurnal cycle. The recent data indicate that impaired melatonin production is involved in several cardiovascular pathologies including hypertension and ischemic heart disease. However, the mechanisms of melatonin effect on cardiovascular system are still not completely understood. The activation of melatonin receptors on endothelial and vascular smooth muscle cells and antioxidant properties of melatonin could be responsible for the melatonin effects on vascular tone. However, the data from in vitro studies are controversial making the explanation of the melatonin effect on blood pressure in vivo difficult. In vivo, melatonin also attenuates sympathetic tone by direct activation of melatonin receptors, scavenging free radicals or increasing NO availability in the central nervous system. The central and peripheral antiadrenergic action of chronic melatonin treatment might eliminate the mechanisms counter-regulating decreased blood pressure, providing thus additional cardioprotective mechanism. The extraordinary antioxidant activity and antilipidemic effects of melatonin may enhance the modulation of blood pressure by melatonin and probably play the most important role in the amelioration of target organ damage by chronic melatonin treatment. Further investigation of these mechanisms should provide novel knowledge about pathophysiological mechanisms of cardiovascular diseases, additional explanation for their circadian and seasonal variability and potentially generate new impulses for the development of therapeutic arsenal., Ľ. Paulis, F. Šimko., and Obsahuje bibliografii a bibliografické odkazy
Postnatal heart development is characterized by critical periods of heart remodeling. In order to characterize the changes in the lipophilic fraction induced by free radicals, fatty acids and t heir oxidized products, lipofuscin -like pigments (LFP), were investigated. Fatty acids were analyz ed by gas chromatography and LFP were studied by fluorescence techniques. A fluorophore characterized by spectral methods was further resolved by HPLC. Major changes in the composition of fatty acids occurred immediately after birth and then during maturation. Fluorescence of LFP changed markedly on postnatal days 1, 4, 8, and 14, and differed from the adult animals. LFP comprise several fluorophores that were present since fetal state till adulthood. No new major fluorophores were formed during development, just the abundances of individual fluorophores have been modulated which produced changes in the shape of the spectral arrays. HPLC resolved the fluorophore with excitation maximum at 360 nm and emission maximum at 410 nm. New chromatographically distinct species appeared immediately on postnatal day 1, and then on days 30 and 60. Consumption of polyunsaturated fatty acids immediately after birth and subseque nt formation of LFP suggests that oxidative stress is involved in normal heart development., J. Wilhelm, J. Ivica, Z. Veselská, J. Uhlík, L. Vajner., and Obsahuje bibliografii
Flavonoids, a group of phenolic compounds found naturally in fruit, vegetables, nuts, flowers, seeds and bark are an integral part of the human diet. They have been reported to exhibit a wide range of biological effects, including anti-ischemic, antiplatelet, antineoplastic, antiinflammatory, antiallergic, antilipoperoxidant or gastroprotective actions. Furthermore, flavonoids are potent antioxidants, free radical scavengers and metal chelators, and inhibit lipid peroxidation. Oxidative modification of low-density lipoproteins (LDLs) is believed to play a crucial role in atherogenesis. Epidemiological studies have shown that the consumption of fruits and vegetables, and regular red wine consumption is related with a reduced risk of cardiovascular diseases., G. Mojžišová, M. Kuchta., and Obsahuje bibliografii
Melatonin has been shown to play a role in antioxidative defence. We therefore studied its effect on oxidative damage to the rat cerebral cortex evoked by painful stimulation and immobilization-induced stress. Moreover, the effect of melatonin on chronic pain perception was examined. Rats were injected with either a high dose of melatonin (100 mg/kg i.p.) or a vehicle for five days and were subjected to painful stimulation or immobilization stress 30 min after the treatment. To determine the degree of oxidative stress, the levels of free radicals, thiobarbituric acid reactive substances (TBARS) as indicators of lipid peroxidation and glutathione peroxidase (GSHPx) were estimated in somatosensory cortex. Pain perception was measured by the tail-flick and plantar test. Melatonin reduced the level of TBARS previously increased by painful stimulation. Melatonin also exhibited a slight analgesic effect in those animals exposed to painful stimulation but its role in free radical scavenging did not contribute to this effect., I. Pekárková, S. Parara, V. Holeček, P. Stopka, L. Trefil, J. Racek, R. Rokyta., and Obsahuje bibliografii
The ability of stobadine to prevent gastric mucosal injury was tested in rat gastric ischaemia induced by 30 min clamping of the coeliac artery with subsequent 30 min reperfusion. Serious injury of gastric mucosa (macroscopic and microscopic) and the increase of microvascular permeability was found after ischaemia/reperfusion in rats without stobadine. After oral pretreatment with stobadine (5 mg.kg-1, 30 min before surgery), the development of gastric mucosal lesions and changes of vascular permeability were significantly decreased.
Photothrombotic model of ischemia (PT) is based on free radical-mediated endothelial dysfunction followed by thrombosis. Free radicals are also involved in hypoxic preconditioning. We tested the sensitivity of PT to preconditioning with hypobaric hypoxia and to pretreatment with melatonin. In adult Wistar rats, after intravenous application of Rose Bengal, a stereo-tactically defined spot on the denuded skull was irradiated by a laser for 9 min. The first experimental group underwent hypobaric hypoxia three days before irradiation. In the second experimental group, melatonin was applied intraperitoneally one hour before irradiation. Three days after irradiation, animals were sacrificed, the brains perfused, and stained with TTC. Ischemic lesions were divided into grades (I, II, III). In the control group (where no manipulation preceded photothrombosis), most animals displayed deep damage involving the striatum (grade III). The group pre-exposed to hypoxia showed similar results. Only 28.57 % of the melatonin pretreated animals exhibited grade III lesions, and in 57.14 % no signs of lesions were detected. Pre-exposure to hypoxia was not protective in our model. Pretreatment with melatonin lead to a significant reduction of the number of large ischemic lesions. This result is probably caused by protection of endothelial cells by melatonin., I. Matějovská, K. Bernášková, D. Krýsl, J. Mareš., and Obsahuje bibliografii a bibliografické odkazy
Catalase is an antioxidant enzyme the activity of which is crucial for the protection against damage caused by reactive oxygen species. The –262C>T polymorphism in the promoter region of catalase gene was found to be associated with altered catalase levels. In this study, peripheral blood mononuclear cells catalase activity was measured after H2 O2-induced oxidative stress. C/T and T/T genotypes were associated with the decrease of catalase levels in contrast to C/C donors who had elevated catalase activity in the presence of 0.4 and 0.7 mM H2 O2. Genotypedependent response of catalase activity to oxidative stress might be related to the predisposition of catalase mutant allele carriers to disorders mediated by oxidative stress., A. V. Komina, ... [et al.]., and Obsahuje seznam literatury
Reactive oxygen species (ROS) have been implicated in the mechanism of postischemic contractile dysfunction, known as myocardial stunning. In this study, we examined protective effects of antioxidant enzymes, superoxide dismutase (SOD) and catalase, against ischemia/reperfusion-induced cardiac dysfunction and inhibition of Na+,K+-ATPase activity. Isolated Langendorff-perfused rabbit hearts were subjected to 15 min of global normothermic ischemia followed by 10 min reperfusion. The hearts treated with SOD plus catalase did not show significant recovery of left ventricular (LV) end-diastolic pressure compared with untreated ischemic reperfused hearts. Treatment with antioxidants had no protective effects on developed LV pressure or its maximal positive and negative first derivatives (±LVdP/dt). Myocardial stunning was accompanied by significant loss in sarcolemmal Na+,K+-ATPase activity and thiol group content. Inhibition of enzyme activity and oxidation of SH groups were not prevented by antioxidant enzymes. These results suggest that administration of SOD and catalase in perfusate do not protect significantly against cardiac dysfunction in stunned rabbit myocardium., P. Kaplán, M. Matejovičová, P. Herijgers, W. Flameng., and Obsahuje bibliografii a bibliografické odkazy
Long-term effects of renal denervation (DNX) commonly include a decrease in blood pressure (BP), observed in both normotensive animals and various models of hypertension. On the other hand, short term BP re sponses vary. We examined how post-DNX increase in BP observed in this study depends on baseline metabolic and functional status of an imals, with a special interest for the role of oxidative stress. Anesthetized Wistar rats on standard (STD), low-sodium (LS) or high-sodium (HS) diet were used, untreated or pre-treated with tempol, a superoxide scavenger, or N(omeg a)-propyl-L-arginine (L-NPA), an inhibitor of neuronal NOS (nNOS). Early BP and renal hemodynamic responses were examined to right- and then left- side DNX performed using an own relatively non-invasive technique. Left kidney cortical, outer- and inner-medullary blood flows (CBF, OMBF, IMBF) were co ntinuously recorded as laser- Doppler fluxes. Sequential denervat ions significantly increased BP to final 19 %, 12 %, and 6 % above control level in HS, LS, and STD groups, respectively. CBF, a measure of total renal perfusion, increased in LS and STD but not in HS rats. Tempol pretreatment prevented the post-denervation BP increase on each diet. Selective inhibition of nNOS prevented BP increase in STD and HS groups, a modest incr ease persisted in LS rats. We propose that enhanced afferent impulsation from intrarenal chemoreceptors related to oxidative stress in the kidney was the background for acute BP increase after DNX. The response was triggered by a release of brain sympatho-excitatory centers from inhibition by renal afferents, this was followed by widespread sympathetic cardiovascular stimulation., A. Walkowska, J. Sadowski, E. Kompanowska-Jezierska., and Obsahuje seznam literatury