The effect of chronic hypercapnia on cardioprotection induced by chronic hypoxia was investigated in adult male Wistar rats exposed to isobaric hypoxia (10 % O2) for three weeks. In the first experimental group, CO2 in the chamber was fully absorbed; in the second group, its level was increased to 4.1 %. Normoxic controls were kept in atmospheric air. Anesthetized open-chest animals were subjected to 20-min LAD coronary artery occlusion and 3-h reperfusion for infarct size determination (TTC staining). Chronic hypoxia alone reduced body weight and increased hematocrit; these effects were significantly attenuated by hypercapnia. The infarct size was reduced from 61.9 ± 2.2 % of the area at risk in the normoxic controls to 44.5±3.3 % in the hypoxic group (P<0.05). Hypercapnia blunted the infarct size-limiting effect of hypoxia (54.8±2.4 %; P<0.05). It is concluded that increased CO2 levels in the inspired air suppress the development of the chronic hypoxia-induced cardioprotective mechanism, possibly by interacting with ROS signalling pathways., J. Neckář, O. Szárszoi, J. Herget, B. Ošťádal, F. Kolář., and Obsahuje bibliografii
The aim of the present study was to test the hypothesis that chronic hypoxia would aggrav ate hypertension in Ren-2 transgenic rats (TGR), a well-defined monogenetic model of hypertension with increased ac tivity of endogenous renin- angiotensin system (RAS). Systolic blood pressure (SBP) in conscious rats and mean arterial pressure (MAP) in anesthetized TGR and normotensive Hannover Sprague-Dawley (HanSD) rats were determined under normoxia that was either continuous or interrupted by two weeks' hypoxi a. Expression, activities and concentrations of individual components of RAS were studied in plasma and kidney of TGR and HanSD rats under normoxic conditions and after exposure to chronic hypoxia. In HanSD rats two weeks' exposure to chroni c hypoxia did not alter SBP and MAP. Surprisingly, in TGR it de creased markedly SBP and MAP; this was associated with substantial reduction in plasma and kidney renin activities and also of angiotensin II (ANG II) levels, without altering angiotensin-converting enzyme (ACE) activities. Simultaneously, in TGR the exposu re to hypoxia increased kidney ACE type 2 (ACE2) activity and angiotensin 1-7 (ANG 1-7) concentrations as compared with TGR under continuous normoxia. Based on these results, we propose that suppression of the hypertensiogenic ACE-ANG II axis in the circulation and kidney tissue, combined with augmentation of the intrarenal vasodilator ACE2-ANG 1-7 axis, is the main mechanism responsible for the blood pressure-lowering effects of chronic hypoxia in TGR., L. Červenka, J. Bíbová, Z. Husková, Z. Vańourková, H. J. Kramer, J. Herget, Š. Jíchová, J. Sadowski, V. Hampl., and Obsahuje bibliografii
We investigated the influence of oxygenation of in vitro lung preparation on the pulmonary vascular reactivity. Small pulmonary vessels isolated from adult male Wistar rats exposed for 4 days to hypoxia (FiO2 = 0.1, group CH) were compared with those of normoxic controls (group N). The bath in the chamber of small vessel myograph was saturated with gas mixture containing either 21 % or 95 % of O2 with 5 % CO2 and we measured the reactions of vessels to acute hypoxic challenge with 0 % O2 or to PGF2α. We did not observe any difference of the contractile responses between both groups when the normoxic conditions were set in the bath. When the bath oxygenation was increased to 95 % O2, the contractions induced by hypoxic challenge and PGF2α decreased in chronically hypoxic rats and did not change in normoxic controls. We hypothesize that reduced reactivity of vessels from hypoxic rats in hyperoxia results from the effect of chronic hypoxia on Ca2+ signaling in the vascular smooth muscle, which is modulated by increased free radical production during the exposure to chronic hypoxia and further hyperoxia., M. Žaloudíková, M. Vízek, J. Herget., and Obsahuje seznam literatury
Chronic hypoxia results in hypoxic pulmonary hypertension characterized by fibrotization and muscularization of the walls of peripheral pulmonary arteries. This vessel remodeling is accompanied by an increase in the amount of lung mast cells (LMC) and the presence of small collagen cleavage products in the vessel walls. We hypothesize that hypoxia activates LMC, which release matrix metalloproteinases (MMPs) cleaving collagen and starting increased turnover of connective tissue proteins. This study was designed to determine whether in vitro hypoxia stimulates production of MMPs in rat LMC and increases their collagenolytic activity. The LMC were separated on the Percoll gradient and then were divided into two groups and cultivated for 24 h in 21 % O2 + 5 % CO2 or in 10 % O2 + 5 % CO2. Presence of the rat interstitial tissue collagenase (MMP-13) in LMC was visualized by immunohistological staining and confirmed by Western blot analysis. Total MMPs activity and tryptase activity were measured in both cultivation media and cellular extracts. Exposure to hypoxia in vitro increased the amount of cells positively labeled by anti-MMP-13 antibody as well as activities of all measured enzymes. The results therefore support the concept that LMC are an important source of increased collagenolytic activity in chronic hypoxia., H. Maxová, J. Novotná, L. Vajner, H. Tomášová, R. Vytášek, M. Vízek, L. Bačáková, V. Valoušková, T. Eliášová, J. Herget., and Obsahuje bibliografii a bibliografické odkazy
Matrix metalloproteinases (MMPs) is a family of proteolytic enzymes involved in remodeling of extracellular matrix. Although proteolytic enzymes are produced by many cell types, mast cells seem to be more important than other types in remodeling of pulmonary arteries during hypoxia. Therefore, we tested in vitro production of MMPs and serine proteases in four cell types (mast cells, fibroblasts, vascular smooth muscle cells and endothelial cells) cultivated for 48 h under normoxic or hypoxic (3 % O2) conditions. MMP-13 was visualized by immunohistochemistry, MMP-2 and MMP-9 were detected by zymography in cell lysates. Enzymatic activities (MMPs, tryptase and chymase) were estimated in the cultivation media. Hypoxia had a minimal effect on total MMP activity in the cultivation media of all types of cells, but immunofluorescence revealed higher intensity of MMP-13 in the cells exposed to hypoxia except of fibroblasts. Tryptase activity was three times higher and chymase activity twice higher in mast cells cultivated in hypoxia than in those cultured in normoxia. Among all cell types studied here, mast cells are the most abundant source of proteolytic enzymes under normoxic and hypoxic conditions. Moreover, in these cells hypoxia increases the production of both specific serine proteases tryptase and chymase, which can act as MMPs activators., H. Maxová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy