Pulmonary hypertension is a group of diseases characterized by elevated pulmonary artery pressure and pulmonary vascular resistance with significant morbidity and mortality. The most prevalent type is pulmonary hypertension secondary to left heart disease (PH-LHD). The available experimental models of PH-LHD use partial pulmonary clamping by technically nontrivial open-chest surgery with lengthy recovery. We present a simple model in which the reduction of the cross-sectional area of the ascending aorta is achieved not by external clamping but by partial intravascular obstruction without opening the chest. In anesthetized rats, a blind polyethylene tubing was advanced from the right carotid artery to just above the aortic valve. The procedure is quick and easy to learn. Three weeks after the procedure, left heart pressure overload was confirmed by measuring left ventricular end-diastolic pressure by puncture (1.3 ± 0.2 vs. 0.4 ± 0.3 mmHg in controls, mean ± SD, P < 0.0001). The presence of pulmonary hypertension was documented by measuring pulmonary artery pressure by catheterization (22.3 ± 2.3 vs. 16.9 ± 2.7 mmHg, P = 0.0282) and by detecting right ventricular hypertrophy and increased muscularization of peripheral pulmonary vessels. Contributions of a precapillary vascular segment and vasoconstriction to the increased pulmonary vascular resistance were demonstrated, respectively, by arterial occlusion technique and by normalization of resistance by a vasodilator, sodium nitroprusside, in isolated lungs. These changes were comparable, but not additive, to those induced by an established pulmonary hypertension model, chronic hypoxic exposure. Intravascular partial aortic obstruction offers an easy model of pulmonary hypertension induced by left heart disease that has a vasoconstrictor and precapillary component.NEW & NOTEWORTHY We present a new, simple model of a clinically important type of pulmonary hypertension, that induced by left heart failure. Left ventricular pressure overload is induced in rats by inserting a blinded cannula into the ascending aorta via carotid artery access. This partial intravascular aortic obstruction, which does not require opening of the chest and prolonged recovery, causes pulmonary hypertension, which has a precapillary and vasoconstrictor as well as a vascular remodeling component.

• MeSH
• aorta * patofyziologie   patologie   MeSH
• arteria pulmonalis patofyziologie   patologie   MeSH
• cévní rezistence MeSH
• hypertrofie pravé komory srdeční patofyziologie   etiologie   MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech * MeSH
• plicní hypertenze * patofyziologie   etiologie   MeSH
• potkani Sprague-Dawley MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• abstrakt z konference MeSH

The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed.

• MeSH
• Evropská unie MeSH
• lidé MeSH
• mezinárodní spolupráce * MeSH
• molekulární biologie organizace a řízení   trendy   MeSH
• oxidace-redukce MeSH
• reaktivní formy kyslíku chemie   metabolismus   MeSH
• signální transdukce MeSH
• společnosti vědecké MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

As with other organ transplants even lung transplantation raises the question of the possibility of the influence of gender on ischemia-reperfusion injury. This is a current topic especially for increasingly utilized method of lung transplantation from non-heart-beating donors, where reperfusion preceded by a period of warm and cold ischemia with subsequent treatment options for lung graft reperfusion. For measurements we used our laboratory previously created and validated animal model for ex vivo lung transplantation. As with other organ systems of our monitoring resulted protective effect of female sex on ischemia reperfusion lung injury. In two of the three parameters that were monitored, we found a significant difference. In females, higher oxygen transfer ability after reperfusion was manifested as well as lower perfusion pressure (vascular compliance). Conversely, weight gain (the development of pulmonary edema) in males was not significant difference from the females. These conclusions could cause further studies leading to influence the selection of appropriate donor grafts.

• MeSH
• cévní rezistence MeSH
• hmotnostní přírůstek MeSH
• krevní tlak MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• plicní nemoci patologie   MeSH
• plicní oběh MeSH
• poddajnost plic MeSH
• pohlavní dimorfismus MeSH
• potkani Wistar MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• reperfuzní poškození patologie   MeSH
• spotřeba kyslíku MeSH
• transplantace plic metody   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Exposure to hypoxia, leading to hypoxic pulmonary hypertension (HPH), is associated with activation of alveolar macrophages (AM). However, it remains unclear how AM participate in this process. There are studies which imply that the AM product monocyte chemoattractant protein-1 (MCP-1) plays an important role. Thus we tested: 1. if the selective elimination of AM attenuates HPH in rats, 2. the correlation of MCP-1 plasmatic concentrations with the presence and absence of AM during exposure to hypoxia, 3. the direct influence of hypoxia on MCP-1 production in isolated AM. We found that experimental depletion of AM attenuated the chronic hypoxia-induced increase in mean pulmonary arterial pressure, but did not affect the serum MCP-1 concentrations. Furthermore, the MCP-1 production by AM in vitro was unaffected by hypoxia. Thus we conclude that AM play a significant role in the mechanism of HPH, but MCP-1 release from these cells is most likely not involved in this process. The increase of MCP-1 accompanying the development of HPH probably originates from other sources than AM.

• MeSH
• alveolární makrofágy sekrece   MeSH
• chemokin CCL2 krev   MeSH
• dichlormethylendifosfonát terapeutické užití   MeSH
• hypoxie komplikace   MeSH
• plicní hypertenze imunologie   prevence a kontrola   MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Pulmonary hypertension is a major complication of respiratory and cardiovascular diseases. This hypertension is triggered by sustained hypoxia resulting in oxidant injury of the wall of peripheral, prealveolar pulmonary vessels, thickening of their walls and an increase in their reactivity to stimuli causing vasoconstriction. Limitation of oxidant injury could be therefore useful in treatment of HPH. Project is aimed at elucidation of mechanisms responsible for increased ROS and NO production during chronic hypoxia, a role of this increase in pathogenesis of HPH and possibility to interfere with this increase in clinically useful way. We plan to use an experimental approach using methods developed for experiments on rats and described in details in our previous publications. In vivo as well as in vitro experiments using cultured tissues and isolated cells are planned.

Plicní hypertenze je závažnou komplikací plicních i srdečních onemocnění. Základním stimulem pro vznik této hypertenze je hypoxie stěny periferních, prealveolárních plicních cév vyvolávající radikálové poškození a ztluštění jejich stěn a zvýšení jejich reaktivity na vazokonstrikční podněty. Omezení radikálového poškození je proto nadějnou cestou terapie hypoxické plicní hypertenze. Projekt je zaměřen na poznání změn produkce reaktivních sloučenin kyslíku a NO během chronické hypoxie, jejich podílu na vzniku a rozvoji hypoxické plicní hypertenze a zjištění způsobů jejich ovlivnění vhodných pro klinické využití. Při řešení projektu budeme používat experimentální metody vhodné pro laboratorní potkany, které jsou na našich pracovištích spolehlivě ověřeny. Experimenty budou prováděny jak "in vivo", tak "in vitro" na tkáňových kulturách a izolovaných buňkách.

• MeSH
• hypoxie MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• onemocnění periferních cév MeSH
• oxid dusnatý analýza   MeSH
• oxidační stres MeSH
• plicní alveoly krevní zásobení   MeSH
• plicní hypertenze MeSH
• reaktivní formy kyslíku analýza   MeSH
• Check Tag
• krysa rodu rattus MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• angiologie
• pneumologie a ftizeologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

Idiopathic pes equinovarus is a congenital deformity of the foot and lower leg defined as a fixation of the foot in adduction, supination, and varus. Although the pathogenesis of clubfoot remains unclear, it has been suggested that fibroblasts and growth factors are involved. To directly analyze the protein composition of the extracellular matrix in contracted tissue of patients with clubfoot. A total of 13 infants with idiopathic clubfoot treated with the Ponseti method were included in the present study. Tissue samples were obtained from patients undergoing surgery for relapsed clubfeet. Contracted tissues were obtained from the medial aspect of the talonavicular joint. Protein was extracted after digestion and delipidation using zip-tip C18. Individual collagenous fractions were detected using a chemiluminescent assay. Amino acid analysis of tissue samples revealed a predominance of collagens, namely collagen types I, III, and VI. The high content of glycine and h-proline suggests a predominance of collagens I and III. A total of 19 extracellular matrix proteins were identified. The major result of the present study was the observation that the extracellular matrix in clubfoot is composed of an additional 16 proteins, including collagens V, VI, and XII, as well as the previously described collagen types I and III and transforming growth factor β. The characterization of the general protein composition of the extracellular matrix in various regions of clubfoot may help in understanding the pathogenesis of this anomaly and, thus, contribute to the development of more efficacious therapeutic approaches.

• MeSH
• aminokyseliny analýza   MeSH
• extracelulární matrix - proteiny metabolismus   MeSH
• kojenec MeSH
• kolagen metabolismus   MeSH
• lidé MeSH
• pes equinovarus metabolismus   patologie   terapie   MeSH
• proteomika metody   MeSH
• transformující růstový faktor beta metabolismus   MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Two mechanisms contribute in the development of pulmonary hypertension in pulmonary embolism (PE) - obstruction of pulmonary blood vessels and vasoconstriction. We hypothesize that hypoxia, increased shear stress and/or activation of gathered leukocytes in the PE may cause a release of reactive oxygen species (ROS). Therefore our aim was to determine the influence of the ROS scavenger Tempol on pulmonary hypertension and to describe NO synthase activity and production of NO oxidative products (NOx) after PE. In general anesthesia sephadex microspheres suspended in PSS were applied in right jugular vein as the pulmonary microembolism. Than we measured in isolated salt solution-perfused lungs the changes in perfusion pressure, activity of NO synthase and NOx plasma concentration in 7 groups of rats: C: control group (n=5), CN: C + sodium nitroprusside (SN) (n=5), EN: PE + SN (n=5), ETN: Tempol + PE + SN (n=5), CL: C + L-NAME (n=5), EL: PE + L-NAME (n=5), ETL: Tempol + PE + L-NAME (n=5). Tempol was applied intraperitoneally before PE. Animals that received Tempol (groups TN, TL) had significantly lower basal perfusion pressure than those which did not receive Tempol (EN, EL). Overall we measured a higher decrease of perfusion pressure than in the control group (C) after application of SN. Administration of L-NAME after PE (EL) increased the pressure more than in the control group (NL). NOx concentration was higher after PE. We found that preventive administration of Tempol decreases the increase in perfusion pressure after PE. PE increased NO release and concentration of NOx.

• MeSH
• aktivace enzymů účinky léků   fyziologie   MeSH
• cyklické N-oxidy farmakologie   terapeutické užití   MeSH
• krevní tlak účinky léků   fyziologie   MeSH
• krysa rodu rattus MeSH
• mikrocirkulace účinky léků   fyziologie   MeSH
• NG-nitroargininmethylester farmakologie   MeSH
• orgánové kultury - kultivační techniky MeSH
• plicní embolie farmakoterapie   metabolismus   MeSH
• plicní oběh účinky léků   fyziologie   MeSH
• potkani Wistar MeSH
• reaktivní formy kyslíku antagonisté a inhibitory   metabolismus   MeSH
• scavengery volných radikálů farmakologie   terapeutické užití   MeSH
• spinové značení MeSH
• synthasa oxidu dusnatého antagonisté a inhibitory   metabolismus   MeSH
• vazokonstrikce účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Lifesaving therapy for patients with end-stage lung disease is lung transplantation. However, there are not enough available donors. A relatively new method of transplantation from non-heart-beating donors (NHBDs) allows the treatment of the lung outside the body and could increase the number of suitable lungs. We have focused on hypercapnic ventilation, which has the possibility of reducing reactive oxygen species damage. We used four experimental and two control groups of adult rats. Each experimental group underwent the protocol of NHBD lung harvesting. The lungs were than perfused in an ex vivo model and we measured weight gain, arterial-venous difference in partial pressure of oxygen and perfusion pressure. We observed that hypercapnic ventilation during reperfusion reduces the development of pulmonary oedema and has a protective effect on the oxygen transport ability of the lungs after warm ischemia. The effect of CO2 on pulmonary oedema and on oxygen transport ability after warm ischemia could be of clinical importance for NHBD transplantation.

• MeSH
• hyperkapnie * MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• potkani Wistar MeSH
• reperfuzní poškození patofyziologie   prevence a kontrola   MeSH
• transplantace plic škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The present study was performed to evaluate the role of intrapulmonary activity of the two axes of the renin-angiotensin system (RAS): vasoconstrictor angiotensin-converting enzyme (ACE)/angiotensin II (ANG II)/ANG II type 1 receptor (AT₁) axis, and vasodilator ACE type 2 (ACE2)/angiotensin 1-7 (ANG 1-7)/Mas receptor axis, in the development of hypoxic pulmonary hypertension in Ren-2 transgenic rats (TGR). Transgene-negative Hannover Sprague-Dawley (HanSD) rats served as controls. Both TGR and HanSD rats responded to two weeks´ exposure to hypoxia with a significant increase in mean pulmonary arterial pressure (MPAP), however, the increase was much less pronounced in the former. The attenuation of hypoxic pulmonary hypertension in TGR as compared to HanSD rats was associated with inhibition of ACE gene expression and activity, inhibition of AT₁receptor gene expression and suppression of ANG II levels in lung tissue. Simultaneously, there was an increase in lung ACE2 gene expression and activity and, in particular, ANG 1-7 concentrations and Mas receptor gene expression. We propose that a combination of suppression of ACE/ANG II/AT₁receptor axis and activation of ACE2/ANG 1-7/Mas receptor axis of the RAS in the lung tissue is the main mechanism explaining attenuation of hypoxic pulmonary hypertension in TGR as compared with HanSD rats.

• MeSH
• angiotensin I metabolismus   MeSH
• angiotensin II metabolismus   MeSH
• angiotensin konvertující enzym metabolismus   MeSH
• arteriální tlak MeSH
• hypoxie komplikace   enzymologie   patofyziologie   MeSH
• modely nemocí na zvířatech MeSH
• peptidové fragmenty metabolismus   MeSH
• plíce enzymologie   MeSH
• plicní hypertenze enzymologie   genetika   patofyziologie   prevence a kontrola   MeSH
• potkani Sprague-Dawley MeSH
• potkani transgenní MeSH
• protoonkogenní proteiny metabolismus   MeSH
• receptor angiotensinu typ 1 metabolismus   MeSH
• receptory spřažené s G-proteiny metabolismus   MeSH
• renin-angiotensin systém * MeSH
• renin genetika   metabolismus   MeSH
• signální transdukce MeSH
• vazodilatace MeSH
• vazokonstrikce MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH