Vaclav Hampl

Vaclav Hampl
Charles University in Prague | CUNI · Department of Physiology (2. LF)

Prof., PhD

About

80
Publications
8,311
Reads
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4,369
Citations
Citations since 2017
8 Research Items
853 Citations
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2017201820192020202120222023020406080100120140
2017201820192020202120222023020406080100120140
2017201820192020202120222023020406080100120140
Additional affiliations
July 1998 - September 2000
September 1991 - August 1996
University of Minnesota Twin Cities
September 1991 - July 1996
Minneapolis Veterans Affairs Hospital
Position
  • Research Associate
Education
September 1980 - March 1990
Charles University in Prague
Field of study
  • Biology, Physiology

Publications

Publications (80)
Article
Pulmonary hypertension is a group of disorders characterized by elevated mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance. To test our hypothesis that combining two drugs useful in experimental pulmonary hypertension, statins and dehydroepiandrosterone sulfate (DHEA S), is more effective than either agent alone, we induced pu...
Article
Animal models are widely used for studying diabetes in translational research. However, methods for induction of diabetes are conflicting with regards to their efficacy, reproducibility and cost. A comparison of outcomes between the diabetic models is still unknown, especially full-term pregnancy.To understand the comparison, we analyzed the strept...
Article
Aims: To elucidate the role of alveolar macrophages (AM) in the pathogenesis of hypoxic pulmonary hypertension (HPH), we tested the effects of sustained hypoxia on AM polarization and on the formation of superoxide by AM in vivo and in vitro. Main methods: Rat AM were obtained by bronchoalveolar lavage. 4-day exposure to hypoxia (10% O2) was car...
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The development of hypoxic pulmonary hypertension is characterized by the structural remodeling of pulmonary arteries. However, the relationship between changes of arterial cells and the extracellular matrix remains unclear. We focused on the evaluation of the non-fibrillar collagen changes in tunica media induced by a four-day exposure to hypoxia...
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Alcohol abuse during pregnancy is a well-known factor in fetal morbidity, including smaller fetal size. We have shown that chronic hypoxia, considered the main pathogenetic factor in intrauterine growth restriction, elevates fetoplacental vascular resistance (and vasoconstrictor reactivity) and thus, presumably, reduces placental blood flow. We thu...
Article
Introduction: Diabetes is a well-known risk factor in pregnancy. Because maternal diabetes involves oxidative stress that is also induced by chronic hypoxia and can alter vascular function, we sought to determine the effects of chronic maternal hyperglycemia on the fetoplacental vasculature in rats and to compare it with the effects of chronic hyp...
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A common problem in management of polytrauma - a simultaneous injury to more than one organ or organ system, at least one of them lethal without intervention - is a discrepancy between a relatively good initial state and a serious subsequent development. Since nitric oxide (NO) is produced in high quantities during tissue injury, we assumed that se...
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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 l...
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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 el...
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Background: Patients with injuries to multiple organs or organ systems are in a serious risk of shock, multiorgan failure and death. Although there are scoring systems available to assess the extent of polytrauma and guide the prognosis, their usefulness is limited by their considerably subjective nature. As the production of nitric oxide (NO) by...
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BACKGROUND: Chronic hypoxia elevates vascular resistance on the fetal side of the placenta. However, when a low-viscosity perfusate is used, the increase in resistance caused by chronic hypoxia is relatively small (12 mmHg). In the present study we tested the hypothesis that perfusion with more viscous fluid (blood) will reveal more substantial eff...
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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 (AT(1)) axis, and vasodilator ACE type 2 (ACE2)/angiotensin 1-7 (ANG 1-7)/Mas receptor axis, in the development of h...
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The aim of the present study was to test the hypothesis that chronic hypoxia would aggravate hypertension in Ren-2 transgenic rats (TGR), a well-defined monogenetic model of hypertension with increased activity of endogenous renin-angiotensin system (RAS). Systolic blood pressure (SBP) in conscious rats and mean arterial pressure (MAP) in anestheti...
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The vessels on the fetal side of the placenta differ from most other vascular beds except the lungs in that they respond to acute hypoxia by vasoconstriction. An essential role of calcium influx in the mechanism of this hypoxic fetoplacental vasoconstriction (HFPV) has been shown previously. That finding does not, however, exclude the possible invo...
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Chronic lung hypoxia results in hypoxic pulmonary hypertension. Concomitant chronic hypercapnia partly inhibits the effect of hypoxia on pulmonary vasculature. Adult male rats exposed to 3 weeks hypoxia (Fi(02)=0.1) combined with hypercapnia (Fi(C02)=0.04-0.05) had lower pulmonary arterial blood pressure, increased weight of the right heart ventric...
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Important fetal and perinatal pathologies, especially intrauterine growth restriction (IUGR), are thought to stem from placental hypoxia-induced vasoconstriction of the fetoplacental vessels, leading to placental hypoperfusion and thus fetal undernutrition. However, the effects of hypoxia on the fetoplacental vessels have been surprisingly little s...
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Lungs retrieved from non-heart-beating donors (NHBDs) may alleviate the shortage of suitable organs for transplantation. The critical point is the preservation of lungs during warm ischemia, when severe damage is caused by free radicals. We investigated the effect of ventilation, pre-arrest administration of heparin, and the cell-permeable free rad...
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An increase in fetoplacental vascular resistance caused by hypoxia is considered one of the key factors of placental hypoperfusion and fetal undernutrition leading to intrauterine growth restriction (IUGR), one of the serious problems in current neonatology. However, although acute hypoxia has been shown to cause fetoplacental vasoconstriction, the...
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Chronic hypoxia induces lung vascular remodeling, which results in pulmonary hypertension. Vascular remodeling is associated with collagenolysis and activation of matrix metalloproteinases (MMPs). One of the possible sources of MMPs in hypoxic lung are mast cells. The role of lung mast cell collagenolytic activity in hypoxic pulmonary hypertension...
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The aim of the study was to find out whether administration of selenium (Se) will protect the immature heart against ischemia/reperfusion. The control pregnant rats were fed laboratory diet (0.237 mg Se/kg diet); experimental rats received 2 ppm Na2SeO3 in the drinking water from the first day of pregnancy until day 10 post partum. The concentrati...
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Chronic hypoxia results in pulmonary hypertension due to vasoconstriction and structural remodelling of peripheral lung blood vessels. We hypothesize that vascular remodelling is initiated in the walls of prealveolar pulmonary arteries by collagenolytic metalloproteinases (MMP) released from activated mast cells. Distribution of mast cells and thei...
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Unlike all vascular beds with the exception of the pulmonary circulation, fetoplacental vessels respond to acute hypoxia with vasoconstriction. While this hypoxic fetoplacental vasoconstriction (HFPV) is considered essential in the pathogenesis of intrauterine growth retardation, its mechanism is largely unknown. Hypoxia inhibits potassium channels...
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Pathogenesis of hypoxic pulmonary hypertension is initiated by oxidative injury to the pulmonary vascular wall. Because nitric oxide (NO) can contribute to oxidative stress and because the inducible isoform of NO synthase (iNOS) is often upregulated in association with tissue injury, we hypothesized that iNOS-derived NO participates in the pulmonar...
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Exposure to chronic hypoxia results in hypoxic pulmonary hypertension (HPH). In rats HPH develops during the first two weeks of exposure to hypoxia, then it stabilizes and does not increase in severity. We hypothesize that free radical injury to pulmonary vascular wall is an important mechanism in the early days of the hypoxic exposure. Thus antiox...
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Some effects of perinatal hypoxia on pulmonary circulation are permanent. Since pulmonary vascular sensitivity to hypoxia in adults differs between sexes, we hypothesized that gender-based variability also exists in the long-term effects of perinatal hypoxia. Rats spent 1 wk before and 1 wk after birth in hypoxia (12% O2) and then lived in normoxia...
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Chronic hypoxia induces lung vascular remodeling, which results in pulmonary hypertension. We hypothesized that a previously found increase in collagenolytic activity of matrix metalloproteinases during hypoxia promotes pulmonary vascular remodeling and hypertension. To test this hypothesis, we exposed rats to hypoxia (fraction of inspired oxygen =...
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Pathogenesis of pulmonary hypertension includes vascular smooth muscle cell membrane depolarisation and consequent calcium influx. Usually, calcium-gated potassium channels are activated under such conditions and repolarise the membrane. However, in pulmonary hypertension they are downregulated. The authors hypothesised that pharmacological augment...
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Fetal to maternal blood flow matching in the placenta, necessary for optimal fetal blood oxygenation, may occur via hypoxic fetoplacental vasoconstriction (HFPV). We hypothesized that HFPV is mediated by K(+) channel inhibition in fetoplacental vascular smooth muscle, as occurs in several other O(2)-sensitive tissues. With the use of an isolated hu...
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Renal arteries (RAs) dilate in response to hypoxia, whereas the pulmonary arteries (PAs) constrict. In the PA, O2 tension is detected by an unidentified redox sensor, which controls K+ channel function and thus smooth muscle cell (SMC) membrane potential and cytosolic calcium. Mitochondria are important regulators of cellular redox status and are c...
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ABSTRACT Hypoxic,pulmonary ,vasoconstriction (HPV) is initiated ,by the ,inhibition of several ,4- aminopyridine (4-AP)-sensitive, voltage-gated, K+ channels (Kv). Several O 2-sensitive candidate channels (Kv1.2, Kv1.5, Kv2.1, and Kv3.1b) have been proposed, based on similarities between,their characteristics in expression ,systems and the properti...
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The anorexic agent fenfluramine considerably increases the risk of primary pulmonary hypertension. The mechanism of this effect is unknown. The appetite-reducing action of fenfluramine is mediated by its interaction with the metabolism of serotonin [5-hydroxytryptamine (5-HT)] in the brain. We tested the hypothesis that the pulmonary vasoconstricti...
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Chronic hypoxia causes pulmonary hypertension, the mechanism of which includes altered collagen metabolism in the pulmonary vascular wall. This chronic hypoxic pulmonary hypertension is gradually reversible upon reoxygenation. The return to air after the adjustment to chronic hypoxia resembles in some aspects a hyperoxic stimulus and we hypothesize...
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Chronic pulmonary hypertension is a serious complication of a number of chronic lung and heart diseases. In addition to vasoconstriction, its pathogenesis includes injury to the peripheral pulmonary arteries leading to their structural remodeling. Increased pulmonary vascular synthesis of an endogenous vasodilator, nitric oxide (NO), opposes excess...
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One of the most important differences between the pulmonary and systemic circulation is a considerably lower blood pressure and hemodynamic resistance in the pulmonary circulation. After the discovery of the endogenous vasodilatator, nitric oxide (NO), it had been assumed that pulmonary vasculature is characterized by a high tonic NO production, wh...
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Anorectics (appetite-suppressant drugs) are frequently requested by patients. Their usage, however, can have serious, life-threatening side effects, such as pulmonary hypertension and valve defects. The association of anorexigen use with pulmonary hypertension was first detected at the end of the sixties. Back than, the incidence of pulmonary hyper...
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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 (approximately 12 weeks...
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Postnatal adaptation of the pulmonary circulation is mediated partly by endothelium-derived nitric oxide (NO). Recent studies have demonstrated that inhaled NO causes selective and sustained vasodilation in infants with persistent pulmonary hypertension of the newborn. Because the short half-life of NO limits its clinical application, we hypothesiz...
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Hypoxia initiates pulmonary vasoconstriction (HPV) by inhibiting one or more voltage-gated potassium channels (Kv) in the pulmonary artery smooth muscle cells (PASMCs) of resistance arteries. The resulting membrane depolarization increases opening of voltage-gated calcium channels, raising cytosolic Ca2+ and initiating HPV. There are presently nine...
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Nitric oxide (NO) is a simple molecule causing vasodilation. It is synthesized endoge- nously by a number of cell types including the vascular endothelium. In contrast to the systemic vessels, where a continuous NO production contributes significantly to the ba- sal tone regulation, resting NO synthesis is minimal in a healthy pulmonary circulation...
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Glucocorticoid receptor stimulation increases vasoreactivity of isolated, physiological salt solution-perfused rat lungs. The present study tested whether adrenalectomy would affect the vascular effects of acute and chronic hypoxia in blood-perfused lungs in vitro and in vivo. The dose-pressor response to ventilation hypoxia was significantly depre...
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The appetite suppressant aminorex fumarate is thought to have caused an epidemic of pulmonary hypertension in Europe in the 1960s. More recently, pulmonary hypertension has been described in some patients taking other amphetamine-like, anorexic agents: fenfluramine and its d-isomer, dexfenfluramine. No mechanism has been demonstrated that might acc...
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Angiopeptin is an analog of somatostatin-14, which has been found to inhibit cellular proliferation in several models of systemic vascular injury. As proliferation plays a major role in pulmonary hypertension, we examined the hypothesis that angiopeptin would inhibit the development of chronic hypoxic pulmonary hypertension in the rat. Angiopeptin...
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Nitric oxide (NO) exists in the human breath, but little is known about its site of origin or enzyme source. The aims of this study were to locate the main site of NO release into human breath and to decide whether the inducible isoform of NO synthase (iNOS) and nasal bacteria contribute to breath NO. Using a chemiluminescence assay, NO levels were...
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Inhaled-nitric oxide (NO) is a selective pulmonary vasodilator in short-term clinical studies. Use of NO inhalation in chronic pulmonary hypertension is complicated by potential problems with ambulatory NO delivery. We hypothesized that long-term infusion of NO solution into the central venous circulation, which did not suffer from this drawback, m...
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The cellular mechanisms that determine differences in reactivity of arteries of varying size and origin are unknown. We evaluated the hypothesis that there is diversity in the distribution of K+ channels between vascular smooth muscle (VSM) cells within a single segment of the pulmonary arteries (PAs) and that there are differences in the prevalenc...
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Inhaled nitric oxide (NO) is a selective pulmonary vasodilator, but its use has been restricted almost exclusively to the intensive care setting due to the complexity of its delivery. NO/nucleophile adducts, such as diethylenetriamine/NO (DETA/NO), spontaneously release NO in aqueous solutions. We hypothesized that a nebulized DETA/NO (half-time of...
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Dithionite is a powerful reducing agent used to deoxygenate hemoglobin and create anaerobic conditions in vitro. Recently, dithionite has been used as a convenient means of creating "hypoxia" in experiments studying the O2 sensor in the pulmonary circulation and carotid body. We evaluated the hypothesis that hypoxia created by hypoxic ventilation a...
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There is indirect, contradictory evidence both for increased and reduced synthesis of the endothelium-derived vasodilator, nitric oxide, in the pulmonary circulation during acute hypoxia. Therefore, we decided to directly measure the effect of acute hypoxia on nitric oxide production by cultured pulmonary endothelium. Because increases in the intra...
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I would like to comment on the recent article on nitric oxide by Kam and Govender (Anaesthesia 1994; 4 9 515-21). The authors state, with reference to the study of Liu et al. [l], that diminished nitric oxide activity has been demonstrated in an isolated perfused rat lung model with chronic hypoxia. This section of the review is confused in several...
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Mechanical properties of the adult pulmonary vasculature are affected by perinatal experience of hypoxic pulmonary hypertension. In the present study, we followed the long-term effects of perinatal pulmonary hypertension induced by means other than hypoxia in rats. Daily injections of indomethacin (1 mg.kg-1 body weight (BW)) were given to the part...
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Nitric oxide (NO) is an endogenous vasodilator and inhaled NO is a promising therapeutic agent for the treatment of pulmonary hypertension. However, NO's mechanism of action is not completely understood. Previous studies have shown that NO increases intracellular levels of cyclic guanosine 3',5'-monophosphate (cGMP) and that leads to activation of...
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Nitric oxide (NO) is a vasodilator, neurotransmitter, and inflammatory mediator which is unstable at physiologic O2 tensions. NO's susceptibility to oxidation accounts for its short biological half-life in vivo and greatly complicates its measurement. Measuring NO requires an understanding of the redox reactions and partitioning that determine its...
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Nitric oxide (NO)-induced relaxation is associated with increased levels of cGMP in vascular smooth muscle cells. However, the mechanism by which cGMP causes relaxation is unknown. This study tested the hypothesis that activation of Ca-sensitive K (KCa) channels, mediated by a cGMP-dependent protein kinase, is responsible for the relaxation occurri...
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The role of EDNO in the PHT has been primarily evaluated in animals, with few human studies. Most research has focused on the chronic hypoxic form of PHT. With these limitations in mind, we conclude that basal pulmonary EDNO synthesis is preserved or increased in PHT. Although this EDNO up-regulation seems to reduce the severity of PHT, its relativ...
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The hypothesis that the endothelium-derived relaxing factor/nitric oxide (EDNO) activity is elevated in chronic hypoxic pulmonary hypertension (CH-PHT) was tested using isolated Krebs-albumin-perfused rat lungs. Concentration of the EDNO decomposition products (NOx) in the lungs' effluent was measured by a modified chemiluminescence assay. The func...
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Inhibition of endothelium-derived nitric oxide (EDNO) synthesis causes systemic hypertension. The effects of EDNO inhibition on vascular tone in the low-pressure pulmonary circuit are more controversial. This study tested the hypothesis that basal EDNO synthesis plays a less important role in determining resting tone in the lung than in the kidney....
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Thrombin contracts vascular smooth muscle and stimulates its proliferation. Using a specific thrombin inhibitor, hirudin, we studied whether thrombin contributes to the pulmonary vasoconstriction and vascular proliferation that occurs in pulmonary hypertension. Hirudin was infused intravenously (0.2 mg/h/kg) by minipumps in nine rats during a 3-wk...
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It has been suggested that chronic hypoxic pulmonary hypertension results from chronic hypoxic inhibition of endothelium-derived relaxing factor (EDRF) synthesis. We tested this hypothesis by studying whether chronic EDRF inhibition by N omega-nitro-L-arginine methyl ester (L-NAME) would induce pulmonary hypertension similar to that found in chroni...
Chapter
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The vascular endothelium and smooth muscle exist in close apposition yet they have opposing responses to stimuli which increase free cytosolic calcium concentration, [Ca2+]i. Stimuli which increase [Ca2+]i in the endothelium initiate synthesis of vasodilators, such as prostacyclin and nitric oxide; increases in [Ca2+]i elicits vasoconstriction of s...
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Hyperlipidemia impairs endothelium derived relaxing factor (EDRF) in systemic vessels. To test the hypothesis that the pulmonary circulation is less prone to such impairment, we compared isolated lungs, pulmonary artery rings, and aortic rings of hereditary hyperlipidemic JCR:LA-cp/cp (corpulent) rats with their genetically relevant controls, JCR:L...
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Arginine analogs are commonly used as inhibitors of the synthesis of endothelium-derived relaxing factor, nitric oxide. However, their effect on nitric oxide levels is rarely measured. Using a chemiluminescence assay for nitric oxide, we found that NG-monomethyl-L-arginine enhanced, rather than reduced, nitric oxide synthesis in pulmonary arterial...
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Pneumonia was induced in rats by instillation of carrageenin (0.5 ml of 0.7% solution) into the trachea. Three or four days after instillation, the lungs were isolated, perfused with blood of healthy rat blood donors, and ventilated with air + 5% CO2 or with various hypoxic gas mixtures. Pulmonary vascular reactivity to acute hypoxic challenges was...
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To test whether the effect of almitrine on hypoxic pulmonary vasoconstriction was dose-dependent, two series of experiments were performed on isolated rat lungs perfused with constant flow of blood. In the first series, the effects of different doses of almitrine on perfusion pressure were measured. Baseline perfusion pressure was not changed by so...
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Oxygen tension is known to control the pulmonary vascular tone. We reviewed three hypotheses that try to explain the mechanism whereby hypoxia is sensed in the lung tissue. The first hypothesis concerns the role of the oxygen binding hemoprotein cytochrome P-450. Studies using various inhibitors and activators of cytochrome P-450 show that this enz...