A short review on the role of endothelium and nitric oxide (NO) in experimental hypertension is presented in the light of the literature and our own recent findings. Based on these data, it is concluded that even though there is a lot of evidence in favor of the primary and causal association of endothelial dysfunction and NO in experimental hypertension, it seems still more plausible that they are causative in some types of hypertension only. Our own experience rather speaks for a secondary but still an important participation of endothelium in the maintenance and further elevation of high blood pressure. Endothelium plays a key role in the development of organ damages in hypertension., H. Vapaatalo, E. Mervaala, M.-L. Nurminen., and Obsahuje bibliografii
The prevalence of obesity is increasing worldwide at an alarming rate in both developed and developing countries. Obesity is a chronic complex disease of multifactorial origin resulting from a long-term positive energy balance, in which both genetic and environmental factors are involved. Genetically prone individuals are the first to accumulate fat in the present obesogenic environment. Obesity increases the risks of type 2 diabetes, hypertension, cardiovascular disease, dyslipidemia, arthritis, and several cancers and reduces the average life expectancy. Implementation of effective strategies in prevention and management of obesity should be come an important target in health care systems. Weight changes throughout life depend on the interaction of behavioral, genetic and environmental factors. Weight loss in response to weight management shows a wide range of interindividual variation which is largely influenced by genetic determinants. The strong control of weight loss by genotype was confirmed by twin and family studies. Recently, special attention has been paid to nutritional, hormonal, psychobehavioral and genetic factors which can predict the response to weight reduction programme. In this article currently available data on the role of obesity candidate gene polymorphisms in weight loss and maintenance are reviewed. It is believed that an elucidation of the genetic component in the prognosis of weight management could assist in the development of more effective and individually tailored therapeutic strategies., V. Hainer, H. Zamrazilová, J. Spálová, I. Hainerová, M. Kunešová, B. Aldhoon, B. Bendlová., and Obsahuje bibliografii a bibliografické odkazy
The role of L-DOPA in spinal nociceptive reflex activity has been re-evaluated. In high spinal ca ts, with supraspinal loops being excluded, the onset of reflex facilitation induced by noxious radiant heat is delayed after injection of L-DOPA by 4 to 10 s, i.e. the early component of nociceptive reflex facilitation is blocked, while the late component persisted. Further investigations have shown that the early component of reflex facilitation induced by noxious radiant heat is mediated by Aδ-fibres and the late component by C-fibres. Therefore, it can be assumed that L-DOPA, like opioids, preferentially blocks the transmission in nociceptive reflex pathways from Aδ-fibres., E. D. Schomburg, P. Dibaj, H. Steffens., and Obsahuje bibliografii a bibliografické odkazy
Gastric mucus plays an important role in gastric mucosal protection. Apart from its “barrier” function, it has been demonstrated that mucus protects gastric epithelial cells against toxic oxygen metabolites derived from the xanthine/xanthine oxidase system. In this study, we investigated the effect of malotilate and sucralfate (mucus production stimulators) and N-acetylcysteine (mucolytic agent) on ischemia/reperfusion-induced gastric mucosal injury. Gastric ischemia was induced by 30 min clamping of the coeliac artery followed by 30 min of reperfusion. The mucus content was determined by the Alcian blue method. Sucralfate (100 mg/kg), malotilate (100 mg/kg), and N-acetylcysteine (100 mg/kg) were given orally 30 min before surgery. Both sucralfate and malotilate increased the mucus production in control rats. On the other hand, N-acetylcysteine significantly decreased mucus content in control (sham) group. A significant decrease of mucus content was found in the control and the N-acetylcysteine pretreated group during the period of ischemia. On the other hand, sucralfate and malotilate prevented the decrease the content of mucus during ischemia. A similar result can be seen after ischemia/reperfusion. In the control group and N-acetylcysteine pretreated group a significant decrease of adherent mucus content was found. However, sucralfate and malotilate increased mucus production (sucralfate significantly). Sucralfate and malotilate also significantly protected the gastric mucosa against ischemia/reperfusion-induced injury. However, N-acetylcysteine significantly increased gastric mucosal injury after ischemia/reperfusion. These results suggest that gastric mucus may be involved in the protection of gastric mucosa after ischemia/reperfusion., J. Mojžiš, R. Hegedüšová, L. Mirossay., and Obsahuje bibliografii
Adaptation to hypoxia is beneficial in cardiovascular pathology related to NO shortage or overproduction. However, the question about the influence of adaptation to hypoxia on NO metabolism has remained open. The present work was aimed at the relationship between processes of NO production and storage during adaptation to hypoxia and the possible protective significance of these processes. Rats were adapted to intermittent hypobaric hypoxia in an altitude chamber. NO production was determined by plasma nitrite/nitrate level. Vascular NO stores were evaluated by relaxation of the isolated aorta to diethyldithiocarbamate. Experimental myocardial infarction was used as a model of NO overproduction; stroke-prone spontaneously hypertensive rats (SHR-SP) were used as a model of NO shortage. During adaptation to hypoxia, the plasma nitrite/nitrate level progressively increased and was correlated with the increase in NO stores. Adaptation to hypoxia prevented the excessive endothelium-dependent relaxation and hypotension characteristic for myocardial infarction. At the same time, the adaptation attenuated the increase in blood pressure and prevented the impairment of endothelium-dependent relaxation in SHR-SP. The data suggest that NO stores induced by adaptation to hypoxia can either bind excessive NO to protect the organism against NO overproduction or provide a NO reserve to be used in NO deficiency., E. B. Manukhina, S. Yu. Mashina, B. V. Smirin, N. P. Lyamina, V. N. Senchikhin, A. F. Vanin, I. Yu. Malyshev., and Obsahuje bibliografii
The present study was performed to evaluate the role of neuronal nitric oxide synthase (nNOS)-derived nitric oxide (NO) during the developmental phase of hypertension in transgenic rats harboring the mouse Ren-2 renin gene (TGR). The first aim of the present study was to examine nNOS mRNA expression in the renal cortex and to assess the renal functional responses to intrarenal nNOS inhibition by S-methyl-L-thiocitrulline (L-SMTC) in heterozygous TGR and in age-matched transgene-negative Hannover Sprague-Dawley rats (HanSD). The second aim was to evaluate the role of the renal sympathetic nerves in mediating the renal functional responses to intrarenal nNOS inhibition. Thus, we also evaluated the effects of intrarenal L-SMTC administration in acutely denervated TGR and HanSD. Expression of nNOS mRNA in the renal cortex was significantly increased in TGR compared with HanSD. Intrarenal administration of L-SMTC decreased the glomerular filtration rate (GFR), renal plasma flow (RPF) and sodium excretion and increased renal vascular resistance (RVR) in HanSD. In contrast, intrarenal inhibition of nNOS by L-SMTC did not alter GFR, RPF or RVR and elicited a marked increase in sodium excretion in TGR. This effect of intrarenal L-SMTC was not observed in acutely denervated TGR. These results suggest that during the developmental phase of hypertension TGR exhibit an impaired renal vascular responsiveness to nNOS derived NO or an impaired ability to release NO by nNOS despite enhanced expression of nNOS mRNA in the renal cortex. In addition, the data indicate that nNOS-derived NO increases tubular sodium reabsorption in TGR and that the renal nerves play an important modulatory role in this process., L. Červenka, H. J. Kramer, J. Malý, I. Vaněčková, A. Bäcker, D. Bokemeyer, M. Bader, D. Ganten, K. D. Mitchell., and Obsahuje bibliografii
It has been suggested that increase in acute nitric oxide (NO) or cyclic guanosine monophosphate production may be involved in cardioprotection induced by chronic hypoxia (CH). We studied the effect of NO donor molsi domine and phosphodiesterase type 5 inhibitor sildenafil on myocardial ischemia/reperfusion (I/R) injury in rats adapted to CH. Male Wistar rats were exposed to continuous hypoxia in a normobaric chamber (10 % O 2 , 4 weeks). Rats received either saline, mol sidomine (10 mg/kg body weight, i.v.) or sildenafil (0.7 mg/kg body weight, i.v.) 30 min before ischemia. Control rats were kept under normoxia and treated in a corresponding manner. Adaptation to CH increased the myocardial ischemic tolerance. Acute treat ment with either molsidomine or sildenafil significantly reduced infarct size in normoxic rats and further enhanced cardioprotection induced by CH. However, the cardioprotective effect of CH on I/R injury was not additive to the cardioprotection provided b y the drugs., P. Alánová, F. Kolář, B. Ošťádal, J. Neckář., and Obsahuje bibliografii
We studied the response of several parameters related to oxidative stress in the liver of aging rats. Male Wistar rats aged 1.5, 3, 18 and 24 months were used. Livers showed an increase in superoxide anion (O2-) concentration at 1.5 and 18 months of age compared to the 3-month-old group; a decrease in superoxide dismutase (SOD) was seen at 1.5 months and catalase concentrations remained unaltered throughout the aging process. Nitric oxide (NO) progressively declined with age; a significant decrease was particularly apparent at 18 and 24 months of age. Thiobarbituric acid reactive substances (TBARS) decreased significantly at 1.5 months, whereas it increased at 18 and 24 months of age. Concentrations of prostaglandin E2 (PGE2), and adenine nucleotides, and their metabolites, remained unchanged throughout the aging process. Although the mitochondrial damage caused by oxidative stress can result in reduced ATP production and compromised cell function, our results on adenosine nucleotides and their metabolites support the notion that the integrity of mitochondria and enzymatic activity remain mostly unchanged with aging. In conclusion, we observed a significant decrease in the levels of NO in the older groups of rats and hence in its antioxidant activity. This could explain the observed increase in lipid peroxides which suggests an important role for NO in oxidative stress in the liver of older rats., F. Mármol ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Remodeled pulmonary arteries return to normal structural conditions after the increase in pulmonary artery flow resistance is reversed. We studied whether proteolysis of extracellular matrix proteins and apoptosis occur during reversal of remodeling produced by chronic hypoxia in the rat. Main pulmonary arteries were removed at different times during a 10-day period of exposure to 10% O2 and 14 days after return to air. Content and rates of degradation of collagen and elastin as well as immunoreactive collagenase in tissue and isolated mast cells were measured. Immunoblots for collagenase and tissue inhibitor of metalloproteinases (TIMP) were performed. Apoptosis was assessed by cleavage of DNA and TUNEL assay. Excess collagen and elastin present at 10 days of hypoxia decreased to near normal levels after 3-5 days of air. Transient increases in collagenolytic and elastolytic enzyme activities accompanied the rapid decrease in matrix proteins. Mast cells containing collagenase accumulated in remodeled pulmonary arteries, and the active form of collagenase appeared at the time of peak proteolytic activity. TIMP increased during remodeling. Apoptosis was maximal 3 days after return to air. Our results suggest that activation of enzymes, which degrade matrix proteins, and apoptosis play a role in resolution of vascular remodeling., D. J. Riley, S. Thakker-Varia, F. J. Wilson, G. J. Poiani, C. A. Tozzi., and Obsahuje bibliografii
Fertilization process is a very clever and unique process comprising some essential steps resulting in formation of zygote. Tetraspanin CD9 is considered to be a serious candidate molecule participating in these events. The importance of CD9 has been discussed in relation to acrosome reaction, sperm-binding, sperm-penetration, sperm-egg fusion and eventually, egg activation. The abundant expression of CD9 oocyte plasma membrane and the presence of CD9-containing vesicles in the perivitelline space of intact oocytes have been confirmed. Despite the fact that majority of authors analyzed CD9 expressed on oocytes, several studies considered the function of sperm CD9, too. To understand CD9 involvement, various conditions of in vitro fertilization (IVF) assays using polyclonal as well as monoclonal antibodies or knockout mice were carried out. However, ambiguous data have been obtained about the importance of CD9 in sperm-egg binding or fusion. Although the current findings did not prove any hypothesis, the indispensable role of CD9 in fertilization process was not excluded and the precise role of CD9 remains unexplained., J. Jankovičová, M. Simon, J. Antalíková, P. Cupperová, K. Michalková., and Obsahuje bibliografii