This review concerns the role of nitric oxide (NO) in the pathogenesis of different models of experimental hypertension (NO-deficient, genetic, salt-dependent), which are characterized by a wide range of etiology. Although the contribution of NO may vary between different models of hypertension, a unifying characteristic of these models is the presence of oxidative stress that participates in the maintenance of elevated arterial pressure and seems to be a common denominator underlying endothelial dysfunction in various forms of experimental hypertension. Besides the imbalance between the endothelial production of vasorelaxing and vasoconstricting compounds as well as the relative insufficiency of vasodilator systems to compensate augmented vasoconstrictor systems, there were found numerous structural and functional abnormalities in blood vessels and heart of hypertensive animals. The administration of antihypertensive drugs, antioxidants and NO donors is capable to attenuate blood pressure elevation and to improve morphological and functional changes of cardiovascular system in some but not all hypertensive models. The failure to correct spontaneous hypertension by NO donor administration reflects the fact that sympathetic overactivity plays a key role in this form of hypertension, while NO production in spontaneously hypertensive rats might be enhanced to compensate increased blood pressure. A special attention should be paid to the modulation of sympathetic nervous activity in central and peripheral nervous system. These results extend our knowledge on the control of the balance between NO and reactive oxygen species production and are likely to be a basis for the development of new approaches to the therapy of diseases associated with NO deficiency., J. Török., and Obsahuje bibliografii a bibliografické odkazy
Expression of parvalbumin (PV) and transient receptor potential vanilloid (TRPV1) receptors in the lumbar dorsal root ganglion neurons (DRG) was evaluated in control animals and in rats after acute carageenan-induced knee joint inflammation. PV is a calcium binding protein that acts as a calcium buffer, affects intracellular calcium homeostasis and may thus influence signal transduction and synaptic transmission. TRPV1 receptors are viewed as molecular integrators of nociceptive stimuli and modulate spinal cord synaptic transmission beside their function in the peripheral nerve endings. In naive rats, 13 % of the L4 DRG neurons had PV immunopositivity (PV+) and 36 % expressed TRPV1 receptors (TRPV1+). The soma of the PV+ neurons was of medium to large size, while the TRPV1 receptors were expressed in small diameter neurons. The co-localization of the PV and TRPV1 immunoreactivity was minimal (0.2 %). There was no significant change in the PV+ (11 %), TRPV1+ (42 %) and PV+TRPV1+ (0.25 %) expression, or shift in the neuronal size distribution 28 h after the unilateral peripheral inflammation, both when compared to controls and when ipsilateral to contralateral sides were evaluated. Thus under the given experimental conditions, no change in somatic TRPV1 receptors and PV expression in L4 DRG neurons was found., G. Zachařová, J. Paleček., and Obsahuje seznam literatury
The aim of the present study was to examine the effect of prolonged passive smoking (lasting 3 weeks) on plasma catecholamine levels and reactivity of isolated rabbit arteries. Plasma noradrenaline, adrenaline and dopamine levels were determined radioenzymatically. Isolated rings of the thoracic aorta and carotid artery were suspended in organ chambers and connected to a force transducer for the recording of isometric tension. Plasma noradrenaline levels were found to be significantly elevated in rabbits subjected to passive smoking for 3 weeks. Plasma adrenaline and dopamine levels were not changed. Transmural nerve stimulation of arterial rings evoked frequency-dependent contractions. Prolonged passive smoking did not affect neurogenic contractions of the arteries tested. On the other hand, endothelium-dependent relaxations of phenylephrine-precontracted arteries were significantly impaired. Furthermore, hypertrophy of the left ventricle was observed. In conclusion, passive smoking impairs endothelium-dependent relaxations but not neurogenic contractions of systemic arteries. The impaired relaxations of arteries may be, at least in part, mediated through the degradation of released nitric oxide by superoxide anions derived from cigarette smoke., J. Török, A. Gvozdjáková, J. Kucharská, I. Balažovjech, S. Kyselá, F. Šimko, J. Gvozdják., and Obsahuje bibliografii
The pathological potential of glial cells was recognized already by Rudolf Virchow, Santiago Ramon y Cajal and Pio Del Rio-Ortega. Many functions and roles performed by astroglia in the healthy brain determine their involvement in brain diseases; as indeed any kind of brain in sult does affect astrocytes, and their performance in pathological conditions, to a very large extent, determines the survival of the brain parenchyma, the degree of damage and neurological defect. Astrocytes being in general responsible for overall brain homeostasis are involved in virtually every form of brain pathology. Here we provide an overview of recent developments in identifying the role and mechanisms of the pathological potential of astroglia., A. Chvátal, M. Anděrová, H. Neprašová, I. Prajerová, L. Benešová, O. Butenko, A. Verkhratsky., and Obsahuje bibliografii a bibliografické odkazy
a1_The modern concept of causality of diseases emphasizes the study of natural defense functions of the organism and possibilities of influencing them, which will lead to effective prevention of these diseases. A great deal of information has been obtained on the system growth hormone (GH)/insulin-like growth factor (IGF)-I, which is of quite fundamental importance for the integrity of the organism. A dysbalance of the system may be the cause of diseases of the neonatal period, as well as diseases associated with aging. In old age, the synthesis of the crucial peptide system, IGF-I, declines as well as the sensitivity of tissues to this hormone. At the same time the changes in the expression of IGF-binding proteins (IGFBP) occur. Systemic growth factors are present in measurable concentrations in the circulation, they are, however, taken up or synthesized by some tissues, where they act as local cellular regulators. IGF-I is produced by many tissues, including bones under the control of estrogens, growth hormone and the parathyroid hormone. A decline of bone IGF-I in the cortical portion of bones is one of the many mechanisms leading to the development of involutional osteoporosis. Correlation studies, which have provided evidence of a relationship between the IGF system and the building of peak bone mass and its subsequent loss contributed to the understanding of the pathogenesis of this disease. It may be foreseen that the results of intervention studies focused on the effects of the recombinant IGF-I will also influence therapeutic and preventive approaches. Modern antiresorption pharmacotherapy stabilizes or enhances bone density and reduces the risk of fractures. The addition of effective anabolics might increase the effectiveness of treatment by shifting the remodeling equilibrium in favor of formative processes., a2_Because both recombinant GH and IGF-I have certain therapeutic limitations, it is considered to utilize substances which either stimulate endogenous IGF-I production directly in the bone or modulate synthesis and distribution of binding proteins for the peptide. Further new findings related to physiology and pathophysiology of this peptide will contribute to designing new strategies in the prevention of osteoporosis and other serious diseases of old age, such as diabetes, neoplasias or cardiovascular diseases., I. Žofková., and Obsahuje bibliografii
The most dramatic changes in pulmonary circulation occur at the time of birth. We hypothesized that some of the effects of perinatal hypoxia on pulmonary vessels are permanent. We studied the consequences of perinatal exposure to hypoxia (12 % O2 one week before and one week after birth) in isolated lungs of adult male rats (~12 weeks old) perfused with homologous blood. Perfusion pressure-flow relationship was tilted towards lower pressures in the perinatally hypoxic as compared to the control, perinatally normoxic rats. A non-linear, distensible vessel model analysis revealed that this was due to increased vascular distensibility in perinatally hypoxic rats (4.1±0.6 %/mm Hg vs. 2.3±0.4 %/mm Hg in controls, P = 0.03). Vascular occlusion techniques showed that lungs of the perinatally hypoxic rats had lower pressures at both the pre-capillary and post-capillary level. To assess its role, basal vascular tone was eliminated by a high dose of sodium nitroprusside (20 µM). This reduced perfusion pressures only in the lungs of rats born in hypoxia, indicating that perinatal hypoxia leads to a permanent increase in the basal tone of the pulmonary vessels. Pulmonary vasoconstrictor reactivity to angiotensin II (0.1-0.5 µg) was reduced in rats with the history of perinatal hypoxia. These data show that perinatal hypoxia has permanent effects on the pulmonary circulation that may be beneficial and perhaps serve to offset the previously described adverse consequences., V. Hampl, J. Bíbová, J. Herget., and Obsahuje bibliografii
The 24-hour periodicity of supraventricular (SVPB) and ventricular (VEB) extrasystoles in healthy elderly men (age 49-69 years) was studied at two altitudes during 24 h Holter ECG monitoring. At the low altitude (200 m, n = 26), SVPB were more frequent than VEB. The highest occurrence of SVPB was at 17:00 h, the lowest at 01:00 and 02:00 h (P<0.001). The highest occurrence of VEB was at 09:00 h, the lowest one at 04:00 h (P<0.001). At 1350 m (n=9) the incidence of both SVPB and VEB was approximately twofold higher compared to that at the low altitude (P<0.001). The highest occurrence of SVPB was at 13:00 h, the lowest at 06:00 h (P<0.001). VEB were the most frequent at 10:00 h and 13:00 h, while the lowest frequency was observed at 06:00 h (P<0.001). Our results indicate that the incidence of SVPB and VEB in healthy persons at the moderate altitude is twofold and its periodicity is shifted compared to the low altitude. The cause of increased occurrence of extrasystoles is probably due to β-adrenergic activation of the heart at the higher altitude., Š. Kujaník, M. Sninčák, J.Vokáľ, J. Podracký, J. Koval., and Obsahuje bibliografii
The early postnatal period is characterized by a great plasticity with critical windows in which any inadequate insult or intervention may be able to influence both positively and adversely postnatal growth and development. After birth the rat littermates enter the presuckling period (initial 6 hours terminated by the first nursing), characterized by transition from the amniotic fluid to the air, by the changes of the ambient temperature, by the termination of placental nutrition and by oxidative stress. After this stage the suckling period initiates and the littermates start to consume milk of their mothers. Comsumption of milk culminates on day 15, then decreases and terminates on postnatal day 28. The end of the suckling period and the onset of physiological weaning is determined by the moment when the youngs for the first time consume the solid food together with milk (postnatal day 17 in rats). On day 19 the first intake of drinking water occurs. The weaning period terminates by the last consumption of maternal milk – on postnatal day 28. It is necessary to stress that the duration of early postnatal periods is independent of the changes of body weight. The precise knowledge of individual ontogenetic periods critical for further development is crucial for the prediction and explanation of reactions to various pathogenetic stimuli both under experimental conditions and in clinical medicine., I. Ošťádalová, A. Babický., and Obsahuje seznam literatury
Aldosterone overproduction increases arterial wall stiffness by accumulation of different types of collagen fibres and growth factors. Our previous studies showed that central (aortic) arterial stiffness is increased in primary aldosteronism (PA) independently of concomitant hypertension and that these changes might be reversible after successful adrenalectomy. There is limited data available on the potential impact of mineralocorticoid overproduction on the deterioration of peripheral arterial stiffness. The current study was thus aimed at investigating the effect of aldosterone overproduction on peripheral arterial stiffness assessed by peripheral (femoralankle) pulse wave velocity (PWV) in PA patients compared with essential hypertension (EH) patients. Forty-nine patients with confirmed PA and 49 patients with EH were matched for age, blood pressure, body mass index, lipid profile, and fasting glucose. PWV was obtained using the Sphygmocor applanation tonometer. Both peripheral and central PWV were significantly higher in PA patients compared to EH patients, while clinical blood pressures were similar. Plasma aldosterone level was the main predictor of peripheral PWV in PA. Our data indicate aldosterone overproduction in PA does not preferentially affect central arterial system. Fibroproliferative effect of higher aldosterone levels lead to alteration of central-elastic as well as peripheral-muscular arteries with subsequent increase in its stiffness., J. Rosa ... [et al.]., and Obsahuje seznam literatury
Extensive osteolysis adjacent to orthopedic implants is often associated with wear particles of prosthetic material. The activation of the RANKL/RANK/OPG system is considered to be a likely cause of periprosthetic osteolysis leading to implant failure. The aim of this study was to examine the possible correlation between the clinical extent of osteolysis, the number of wear particles and expression of the osteoclastic mediator RANKL (receptor activator of nuclear factor kappa B ligand) in the tissues aro und aseptically loosened cemented and non-cemented total hip replacements. Periprosthetic tissues were harvested from 59 patients undergoing revision of hip replacement for aseptic loosening. We observed RANKL-positive cells in 23 of our 59 patients, their presence was noted predominantly in tissues with a loosened cemented endoprosthesis. We have found that RANKL is present only in tissues with a large amount of wear debris and predominantly in cases involving loosened cemented implants., D. Veigl, J. Niederlová, O. Kryštůfková., and Obsahuje bibliografii a bibliografické odkazy