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V Hampl

Publications and source records attributed to V Hampl.

At least 19 recordsLinked to original sources
PubMed1995

Hypoxia potentiates nitric oxide synthesis and transiently increases cytosolic calcium levels in pulmonary artery endothelial cells.

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 intracellular free calcium concentration are known to initiate nitric oxide synthesis, we also studied cytosolic calcium levels. We measured the accumulation of the stable nitric oxide metabolite, nitrite, in the fluid used to superfuse the cultured bovine pulmonary artery endothelial cells at an oxygen tension (PO2) of either 20.3 (normoxia) or 4.9 kPa (hypoxia) (152 or 37 mmHg). Intracellular calcium levels were measured with dual-excitation microfluorimetry after loading the cells with the fluorescent calcium indicator, fura 2. Basal NO synthesis, measured as nitrite accumulation over 10 min, was significantly higher under hypoxic than normoxic conditions (8.3 +/- 2.2 versus 4.6 +/- 0.8 nM). Hypoxia transiently increased cytosolic calcium concentration (from 113 +/- 10 to 231 +/- 45 nM). Ryanodine and thapsigargin (which deplete intracellular calcium stores), but not the removal of extracellular calcium, inhibited the hypoxic increase in cytosolic calcium, indicating that it resulted primarily from release of intracellular calcium. Bradykinin-elicited NO synthesis was potentiated by hypoxia. Bradykinin-induced increase in cytosolic calcium was not inhibited by hypoxia. We conclude that hypoxia acutely increases cytosolic calcium levels and basal and bradykinin-stimulated nitric oxide synthesis in pulmonary artery endothelium.

Animals↗
PubMed1994

Nitric oxide and cGMP cause vasorelaxation by activation of a charybdotoxin-sensitive K channel by cGMP-dependent protein kinase.

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 occurring in response to cGMP. In rat pulmonary artery rings, cGMP-dependent, but not cGMP-independent, relaxation was inhibited by tetraethylammonium, a classical K-channel blocker, and charybdotoxin, an inhibitor of KCa channels. Increasing extracellular K concentration also inhibited cGMP-dependent relaxation, without reducing vascular smooth muscle cGMP levels. In whole-cell patch-clamp experiments, NO and cGMP increased whole-cell K current by activating KCa channels. This effect was mimicked by intracellular administration of (Sp)-guanosine cyclic 3',5'-phosphorothioate, a preferential cGMP-dependent protein kinase activator. Okadaic acid, a phosphatase inhibitor, enhanced whole-cell K current, consistent with an important role for channel phosphorylation in the activation of NO-responsive KCa channels. Thus NO and cGMP relax vascular smooth muscle by a cGMP-dependent protein kinase-dependent activation of K channels. This suggests that the final common pathway shared by NO and the nitrovasodilators is cGMP-dependent K-channel activation.

Animals↗
PubMed1994

Increased endothelium-derived NO in hypertensive pulmonary circulation of chronically hypoxic rats.

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 functional significance of basal EDNO production was studied by measuring the vasoconstrictor response to an EDNO synthesis inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME). Reactivity to the endothelium-dependent vasodilator substance P and to exogenous NO was also studied. More NOx was found in effluent from CH-PHT (22.3 +/- 9.8 nM) than control (0.4 +/- 3.9 nM) lungs. The L-NAME-induced vasoconstriction was greater in CH-PHT than in control rats. The sensitivity, but not the maximal vasodilation, to exogenous NO was elevated in CH-PHT. The substance P-induced vasodilation was potentiated in CH-PHT compared with control rats and blocked by L-NAME in both groups. We conclude that basal and agonist-stimulated pulmonary EDNO activity is enhanced in this model of CH-PHT. The EDNO synthesis may play a counterregulatory role in CH-PHT.

Animals↗
PubMed1993

Chronic EDRF inhibition and hypoxia: effects on pulmonary circulation and systemic blood pressure.

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 chronic hypoxia. L-NAME (1.85 mM) was given for 3 wk in drinking water to rats living in normoxia or hypoxia. Unlike chronic hypoxia, chronic L-NAME treatment did not increase pulmonary arterial pressure. Cardiac output was reduced and mean systemic arterial pressure was increased by chronic L-NAME treatment. The vascular pressure-flow relationship in isolated lungs was shifted toward higher pressures by chronic hypoxia and, to a lesser degree, by L-NAME intake. In isolated lungs, vasoconstriction in response to angiotensin II and acute hypoxia and vasodilation in response to sodium nitroprusside were increased by chronic L-NAME treatment in normoxia and chronic hypoxia. Chronic hypoxia, but not L-NAME, induced hypertensive pulmonary vascular remodeling. Chronic supplementation with the EDRF precursor L-arginine did not have any significant effect on chronic hypoxic pulmonary hypertension. We conclude that the chronic EDRF deficiency state, induced by L-NAME, does not mimic chronic hypoxic pulmonary hypertension in our model. In addition, EDRF proved to be less important for basal tone regulation in the pulmonary than in the systemic circulation.

Animals↗
PubMed1992

NG-monomethyl-L-arginine causes nitric oxide synthesis in isolated arterial rings: trouble in paradise.

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 and aortic rings. NG-monomethyl-L-arginine inhibited relaxation to the endothelium-dependent vasodilator A23187 in aortic but not pulmonary arterial rings. In contrast, N omega-nitro-L-arginine did not stimulate nitric oxide synthesis and it inhibited relaxation to A23187 in all rings. We conclude that NG-monomethyl-L-arginine is a partial agonist for nitric oxide synthesis.

Animals↗
PubMed1992

Acute pneumonia reversibly inhibits hypoxic vasoconstriction in isolated rat lungs.

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 significantly lower in lungs of rats with pneumonia than in lungs of controls. The relationship between O2 concentration in the inspired gas and Po2 in the blood effluent from the preparation was shifted significantly to lower Po2 in lungs with pneumonia compared to control ones. These changes were not present in rats allowed to recover for 2-3 weeks after carrageenin instillation. We suppose that blunted hypoxic pulmonary vasoconstriction may contribute to hypoxaemia during acute pulmonary inflammation. Decreased Po2 in the blood effluent from the isolated lungs with pneumonia implies significant increase of oxygen consumption by the cells involved in the inflammatory process.

Acute Disease↗
PubMed1991

Vascular reactivity in isolated lungs of rats with spontaneous systemic hypertension.

Pulmonary vascular reactivity to acute hypoxic challenges and to KCl was measured in isolated blood-perfused lungs of six rats with spontaneous systemic hypertension (SHR) and in six normotensive rats. Baseline perfusion pressure did not differ significantly between SHR (11.0 +/- 1.0 mm Hg) and normotensive controls (12.3 +/- 1.5 mm Hg). Reactivity to acute hypoxia was equal in both groups. In SHR the dose-response of perfusion pressure to KCl was shifted significantly towards lower perfusion pressures as compared with normotensive controls. These results suggest that, even though magnitude of hypoxic pulmonary vasoconstriction is not changed, the mechanism of the response may be altered in SHR.

Analysis of Variance↗
PubMed1991

Possible mechanisms of oxygen sensing in the pulmonary circulation.

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 enzyme affects pulmonary vascular tone. The data are, however, contradictory. The second hypothesis postulates that hypoxia reduces the synthesis of vasodilator oxygen radicals in the lung. This hypothesis is quite well supported by experimental data. The third hypothesis, similarly widely documented, states that slowing of the respiratory chain and altered cellular energetics is crucial for sensing of hypoxia. In this case, however, it is not exactly clear how changes in cellular energetics are connected with vascular tone. The possibility exists that changes in both the cytochrome P-450 activity and in the rate of electrons flow in the respiratory chain may alter the amount of oxygen radicals in the cells and, similarly as in the "oxygen radicals" hypothesis, govern calcium channels through the control of the redox status of these channels.

Oxidation-Reduction↗
PubMed1991

Almitrine in low dose potentiates vasoconstrictor responses of isolated rat lungs to moderate hypoxia.

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 solvent or by 0.25 micrograms.ml-1 almitrine, but it was increased by 0.5 and 2.0 micrograms.ml-1 almitrine. The increase in perfusion pressure in response to 10 min ventilation with hypoxic gas mixture (5% O2) was significantly (p less than 0.05) higher after 0.25 micrograms.ml-1 almitrine (12.0 +/- 0.8 torr) than before addition of the drug (5.43 +/- 1.8 torr). Responses to hypoxia were insignificant after higher doses (0.5 and 2.0 micrograms.ml-1) of almitrine. In the second series of experiments the responses to varying degrees of hypoxia were measured after administration of one dose of almitrine (0.25 micrograms.ml-1). Almitrine, compared to solvent alone, significantly altered the shape of the dose-response curve to hypoxia. Increases in perfusion pressure in response to moderate degrees of hypoxia were potentiated (10% O2: 8.7 +/- 1.8 torr after almitrine, 2.1 +/- 0.6 torr after solvent, p less than 0.05), whereas responses to severe hypoxia (3% O2) were not changed by almitrine. Reactivity to angiotensin II was decreased by 0.25 micrograms.ml-1 almitrine. We conclude that almitrine in low but not in high dose augments pulmonary vasoconstriction induced by mild degrees of hypoxia.

Almitrine↗
PubMed1990

Perinatal hypoxia increases hypoxic pulmonary vasoconstriction in adult rats recovering from chronic exposure to hypoxia.

The possibility that perinatal exposure to hypoxia influences the pulmonary vasculature in adults was tested. Rats born in a hypoxic environment were kept in hypoxia for an additional week after birth. The rats were then raised in atmospheric air, and when adult, they were compared with the rats born and raised in air. Rats (10 wk old) of both groups were exposed to 10% O2 for 2 wk. They were then studied immediately after the exposure and after 2 wk of recovery from the sojourn in the hypoxic environment. The experience of perinatal hypoxia did not affect mean pulmonary arterial blood pressure, right ventricle weight, or the number of muscularized peripheral pulmonary vessels. During exposure to chronic hypoxia in adulthood, both groups developed pulmonary hypertension, which was not affected by previous perinatal hypoxia. The pulmonary vascular responses to acute hypoxic challenges were studied in the preparation of isolated perfused lungs. In both groups of rats, perinatally hypoxic and normoxic, the acute hypoxic vasoconstriction was attenuated immediately after the exposure of adult animals to chronic hypoxia. However, during the recovery from this hypoxic sojourn, the rats born in hypoxia were significantly more reactive to acute lung hypoxia than all other groups of rats studied. It is concluded that the experience of a short period of perinatal hypoxia did not affect the development of hypoxic pulmonary hypertension induced in adulthood. It increased, however, the pulmonary vascular reactivity to acute hypoxic stimuli during the period of recovery from a sojourn in the hypoxic environment in adulthood.

Age Factors↗
PubMed1986

Improved local exhaust control by directed push-pull ventilation system.

Experiments using the directed push-pull ventilation technique were conducted on a general type of local exhaust ventilation installation. The exhaust (pull) system consisted of a square hood, while the push system consisted of one or two slot jets or two round jets. The two slot or round jets were located behind and beside a mannequin (the mannequin simulated the worker's position). The one slot jet was located between the smoke source and the mannequin. Under experimental conditions, the push-pull system reduced the amount of smoke in the mannequin's breathing zone even when the exhaust system volume flow rate necessary for capture of the smoke decreased approximately 50%. Generally, no difference between the slot and round jet control performance was found. The experiments showed that the directed push-pull ventilation system can be used effectively to reduce the contaminant emission into a workroom, if the jets are located so that the eddy currents induced by the worker or other obstructions are minimized or eliminated.

Humans↗
PubMed1986

Use of tracer gas technique for industrial exhaust hood efficiency evaluation--where to sample?

A tracer gas technique using sulfur hexafluoride (SF6) was developed for the evaluation of industrial exhaust hood efficiency. In addition to other parameters, accuracy of this method depends on proper location of the sampling probe. The sampling probe should be located in the duct at a minimum distance from the investigated hood where the SF6 is dispersed uniformly across the duct cross section. To determine the minimum sampling distance, the SF6 dispersion in the duct in fully developed turbulent flow was studied at four duct configurations frequently found in industry: straight duct, straight duct-side branch, straight duct-one elbow, and straight duct-two elbows combinations. Based on the established SF6 dispersion factor, the minimum sampling distances were determined as follows: for straight duct, at least 50 duct diameters; for straight duct-side branch combination, at least 25 duct diameters; for straight duct-one elbow combination, 7 duct diameters; and for straight duct-two elbow combination, 4 duct diameters. Sampling at (or beyond) these distances minimizes the error caused by the non-homogeneous dispersion of SF6 in the duct and contributes to the accuracy of the tracer gas technique.

Air Pollutants, Occupational↗
PubMed1985

Control of wood dust from horizontal belt sanding.

An auxiliary ventilation system has been developed to reduce the wood dust emission from horizontal belt sanders. This system consists of two devices: a hood and a jet stripper. The hood is a narrow low-volume, high-velocity slot hood located between a belt surface and a worktable; the push device is a jet stripper located inside a driven pulley hood opposite the operator site. In combination with a standard sander hood, both devices significantly reduced the wood dust emission into the workroom. Laboratory data were confirmed by field tests conducted at an oscillating edge belt sander at a wood furniture manufacturing plant. These devices work independently of each other and do not interfere with the operator's sanding activity. They do not require special maintenance and are economically feasible.

Dust↗
PubMed1984

Evaluation of industrial local exhaust hood efficiency by a tracer gas technique.

Efficiency of industrial local exhaust ventilation is defined as the ratio of air contaminant quantity captured by the system per unit time to the total contaminant quantity produced by the process per unit time. To date, no direct method exists for this evaluation. This paper describes a tracer gas technique, using sulfur hexafluoride (SF6), which has been developed for the evaluation of local exhaust system efficiency. SF6 was discharged at a known rate into the industrial process generation area. Then, by comparing this quantity to that captured by the exhaust system, as measured in the exhaust duct, hood efficiency is determined. Major advantages of this technique are: The tracer gas technique is able to evaluate directly the hood efficiency. The tracer gas technique is not affected by cross-contamination from nearby industrial processes. The tracer gas technique can be conducted "on site" with minimal interruption of industrial process or interference with workers' duties. The tracer gas, using SF6 is non-toxic. Since SF6 is a gas, this technique may be limited to efficiency evaluation of hoods associated with gases, fumes, vapors, or fine particles.

Evaluation Studies as Topic↗