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Pulmonary Vasoconstriction (pulmonary + vasoconstriction)

Distribution by Scientific Domains

Medical Sciences	80%

Kinds of Pulmonary Vasoconstriction

hypoxic pulmonary vasoconstriction

Selected Abstracts

The Role of K+ Channels in Determining Pulmonary Vascular Tone, Oxygen Sensing, Cell Proliferation, and Apoptosis: Implications in Hypoxic Pulmonary Vasoconstriction and Pulmonary Arterial Hypertension

MICROCIRCULATION, Issue 8 2006
ROHIT MOUDGIL
ABSTRACT Potassium channels are tetrameric, membrane-spanning proteins that selectively conduct K+ at near diffusion-limited rates. Their remarkable ionic selectivity results from a highly-conserved K+ recognition sequence in the pore. The classical function of K+ channels is regulation of membrane potential (EM) and thence vascular tone. In pulmonary artery smooth muscle cells (PASMC), tonic K+ egress, driven by a 145/5 mM intracellular/extracellular concentration gradient, contributes to a EM of about ,60 mV. It has been recently discovered that K+ channels also participate in vascular remodeling by regulating cell proliferation and apoptosis. PASMC express voltage-gated (Kv), inward rectifier (Kir), calcium-sensitive (KCa), and two-pore (K2P) channels. Certain K+ channels are subject to rapid redox regulation by reactive oxygen species (ROS) derived from the PASMC's oxygen-sensor (mitochondria and/or NADPH oxidase). Acute hypoxic inhibition of ROS production inhibits Kv1.5, which depolarizes EM, opens voltage-sensitive, L-type calcium channels, elevates cytosolic calcium, and initiates hypoxic pulmonary vasoconstriction (HPV). Hypoxia-inhibited K+ currents are not seen in systemic arterial SMCs. Kv expression is also transcriptionally regulated by HIF-1, and NFAT. Loss of PASMC Kv1.5 and Kv2.1 contributes to the pathogenesis of pulmonary arterial hypertension (PAH) by causing a sustained depolarization, which increases intracellular calcium and K+, thereby stimulating cell proliferation and inhibiting apoptosis, respectively. Restoring Kv expression (via Kv1.5 gene therapy, dichloroacetate, or anti-survivin therapy) reduces experimental PAH. Electrophysiological diversity exists within the pulmonary circulation. Resistance PASMC have a homogeneous Kv current (including an oxygen-sensitive component), whereas conduit PASMC current is a Kv/KCa mosaic. This reflects regional differences in expression of channel isoforms, heterotetramers, splice variants, and regulatory subunits as well as mitochondrial diversity. In conclusion, K+ channels regulate pulmonary vascular tone and remodeling and constitute potential therapeutic targets in the regression of PAH. [source]

Chronic lung disease: oxygen dogma revisited

ACTA PAEDIATRICA, Issue 2 2001
O D Saugstad
Since the discovery of retrolental fibroplasia, and the role of oxygen in its development, oxygen has been considered a double-edged sword in neonatal medicine, the utmost care being exercised in order not to give too much oxygen (1). However, the important observation that hypoxaemia might induce pulmonary vasoconstriction (2) and airway constriction (3) in infants at risk for bronchopulmonary dysplasia has resulted in only a minor upward adjustment of oxygen supplementation in many neonatal units. Since oxygen toxicity has long been linked not only to retinopathy of prematurity but also to bronchopulmonary dysplasia (4), it is relevant to ask whether an increased FiO2 might have any detrimental effects on babies. [source]

Endothelin receptors blockade blunts hypoxia-induced increase in PAP in humans

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2010
I. Pham
Eur J Clin Invest 2010; 40 (3): 195,202 Abstract Background, Activation of the endothelin-1 (ET-1) pathway may be involved in hypoxia-induced pulmonary vasoconstriction, increase in pulmonary pressure and high altitude pulmonary oedema. Thus, we investigated the effect of the ETA/ETB receptor antagonist, bosentan, on pulmonary artery systolic pressure (PASP) in healthy subjects (n = 10). Design, We used a double-blind, placebo-controlled, randomized, cross-over design to study the effects of a single oral dose of bosentan (250 mg) on PASP after 90-min-exposure to normobaric hypoxia (FiO2 = 0·12). We measured PASP and cardiac output by echocardiography, systolic arterial blood pressure, arterial O2 saturation (SaO2), and blood gases at rest and during a sub-maximal exercise. Results, PASP in normoxia at rest was 23·5 ± 2·7 and during exercise 39·8 ± 11·6 mmHg (P < 0·0001). During the placebo period, hypoxia induced a significant decrease in SaO2, PaO2 and PCO2 and increase in pH. PASP at rest increased significantly: 32·1 ± 3·5 mmHg (P < 0·001 vs. normoxia). Bosentan significantly blunted the hypoxia-induced increase in PASP: bosentan: 27·0 ± 3·3 mmHg, P = 0·002 vs. placebo at rest, but not during exercise: bosentan 39·8 ± 11·6 vs. placebo 43·0 ± 8·5 mmHg, ns. Bosentan had no effect on the hypoxia-induced changes in blood gases, or on cardiac output and systolic arterial blood pressure, which were not modified by hypoxia. Conclusion, A single oral dose of bosentan blunted an acute hypoxia-induced increase in PASP in healthy subjects, without altering cardiac output or systemic blood pressure. [source]

Oxygen sensing in hypoxic pulmonary vasoconstriction: using new tools to answer an age-old question

EXPERIMENTAL PHYSIOLOGY, Issue 1 2008
Gregory B. Waypa
Hypoxic pulmonary vasoconstriction (HPV) becomes activated in response to alveolar hypoxia and, although the characteristics of HPV have been well described, the underlying mechanism of O2 sensing which initiates the HPV response has not been fully established. Mitochondria have long been considered as a putative site of oxygen sensing because they consume O2 and therefore represent the intracellular site with the lowest oxygen tension. However, two opposing theories have emerged regarding mitochondria-dependent O2 sensing during hypoxia. One model suggests that there is a decrease in mitochondrial reactive oxygen species (ROS) levels during the transition from normoxia to hypoxia, resulting in the shift in cytosolic redox to a more reduced state. An alternative model proposes that hypoxia paradoxically increases mitochondrial ROS signalling in pulmonary arterial smooth muscle. Experimental resolution of the question of whether the mitochondrial ROS levels increase or decrease during hypoxia has been problematic owing to the technical limitations of the tools used to assess oxidant stress as well as the pharmacological agents used to inhibit the mitochondrial electron transport chain. However, recent developments in genetic techniques and redox-sensitive probes may allow us eventually to reach a consensus concerning the O2 sensing mechanism underlying HPV. [source]

Gravity is an important determinant of oxygenation during one-lung ventilation

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2010
L. L. SZEGEDI
Background: The role of gravity in the redistribution of pulmonary blood flow during one-lung ventilation (OLV) has been questioned recently. To address this controversial but clinically important issue, we used an experimental approach that allowed us to differentiate the effects of gravity from the effects of hypoxic pulmonary vasoconstriction (HPV) on arterial oxygenation during OLV in patients scheduled for thoracic surgery. Methods: Forty patients with chronic obstructive pulmonary disease scheduled for right lung tumour resection were randomized to undergo dependent (left) one-lung ventilation (D-OLV; n=20) or non-dependent (right) one-lung ventilation (ND-OLV; n=20) in the supine and left lateral positions. Partial pressure of arterial oxygen (PaO2) was measured as a surrogate for ventilation/perfusion matching. Patients were studied before surgery under closed chest conditions. Results: When compared with bilateral lung ventilation, both D-OLV and ND-OLV caused a significant and equal decrease in PaO2 in the supine position. However, D-OLV in the lateral position was associated with a higher PaO2 as compared with the supine position [274.2 (77.6) vs. 181.9 (68.3) mmHg, P<0.01, analysis of variance (ANOVA)]. In contrast, in patients undergoing ND-OLV, PaO2 was always lower in the lateral as compared with the supine position [105.3 (63.2) vs. 187 (63.1) mmHg, P<0.01, ANOVA]. Conclusion: The relative position of the ventilated vs. the non-ventilated lung markedly affects arterial oxygenation during OLV. These data suggest that gravity affects ventilation,perfusion matching independent of HPV. [source]

Divergent effects of ephedrine and phenylephrine on cardiovascular hemodynamics of near-term fetal sheep exposed to hypoxemia and maternal hypotension

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2007
T. Erkinaro
Background:, We hypothesized that the administration of ephedrine and phenylephrine for maternal hypotension modifies cardiovascular hemodynamics in near-term sheep fetuses. Methods:, At 115,136 days of gestation, chronically instrumented, anesthetized ewes with either normal placental function or increased placental vascular resistance after placental embolization were randomized to receive boluses of ephedrine (n = 12) or phenylephrine (n = 12) for epidural-induced hypotension after a short period of hypoxemia. Fetal cardiovascular hemodynamics were assessed by Doppler ultrasonography at baseline, during hypotension and after vasopressor treatment. Results:, During hypotension, fetal PO2 decreased and proximal branch pulmonary arterial and pulmonary venous vascular impedances increased. Additionally, in the embolized fetuses, the time-velocity integral ratio between the antegrade and retrograde blood flow components of the aortic isthmus decreased. These parameters were restored to baseline conditions by ephedrine but not by phenylephrine. With phenylephrine, weight-indexed left ventricular cardiac output and ejection force decreased in the non-embolized fetuses, and the proportion of isovolumetric contraction time of the total cardiac cycle was elevated in the embolized fetuses. Conclusions:, After exposure to hypoxemia and maternal hypotension, ephedrine restored all fetal cardiovascular hemodynamic parameters to baseline. Phenylephrine did not reverse fetal pulmonary vasoconstriction or the relative decrease in the net forward flow through the aortic isthmus observed in fetuses with increased placental vascular resistance. Moreover, fetal left ventricular function was impaired during phenylephrine administration. [source]

Comparison of relaxation responses to multiple vasodilators in TxA2 -analog and endothelin-1-precontracted pulmonary arteries

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2007
C. Piamsomboon
Background:, Peri-operative pulmonary hypertension can lead to right ventricular dysfunction and to an increase in morbidity and mortality. Altered function of the pulmonary vascular endothelium and vasoconstriction play a crucial role in the development of elevated pulmonary vascular resistance. Because pulmonary artery vasoreactivity is dependent on many factors including the constricting agent that precipitated the event therefore the aim of the current study was to investigate the effectiveness of different classes of vasodilator agents to reverse endothelin-1 (ET-1) or thromboxane A2 (TxA2)-induced vasoconstriction in porcine pulmonary artery (PA) in vitro. Methods:, Relaxation responses to vasodilatory drugs were studied in PA precontracted with ET-1 (1 × 10,8 M) or TxA2 analog (U46619, 1 × 10,8 M). All vasodilating drugs were added in a cumulative fashion and isometric tension measurements were obtained using an organ chamber technique. Results:, In both groups relaxation responses to the vasodilators were dose dependent. When ET-1 was used as a constrictor nitroglycerin and milrinone caused nearly complete (80,100%) relaxation, whereas other agents were of limited effectiveness (40,50%). On the other hand, in the vessels constricted with U46619, olprinone, indomethacin, prostaglandin E1 (PGE1), nitroglycerin, milrinone and clevidipine induced complete (90,110%) vasodilatation but brain natriuretic peptide (BNP), l -arginine, and isoproterenol relaxed the vessels maximally by 45,60%. Conclusions:, Nitroglycerin and milrinone are very effective in reversing ET-1 and U46619-induced pulmonary vasoconstriction in vitro. The effectiveness of other drugs studied was dependent on the type of constrictor used. BNP, l -arginine and isoproterenol were shown to have minimal vasodilatory effects in porcine PA. [source]

The Role of K+ Channels in Determining Pulmonary Vascular Tone, Oxygen Sensing, Cell Proliferation, and Apoptosis: Implications in Hypoxic Pulmonary Vasoconstriction and Pulmonary Arterial Hypertension

Multiple Inert Gas Elimination Technique For Determining Ventilation/Perfusion Distributions In Rat During Normoxia, Hypoxia And Hyperoxia

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2001
V Alfaro
SUMMARY 1. The use of the multiple inert gas elimination technique (MIGET) in quantifying ventilation/perfusion distributions (V,A/Q,) in small animals, such as the rat, may cause results to be biased due to haemodilution produced by the large volume of liquid infused intravenously. 2. We tested two methods of administering inert gases in rats using the MIGET: (i) standard continuous intravenous administration of inert gases (method A); and (ii) a new method based on the physicochemical properties of each inert gas (method B). This method included acute simultaneous inert gas administration using three pathways: inhalation, intravenous infusion and rectal infusion. Both MIGET methods were applied to obtain data while breathing three different inspiratory fractions of oxygen (FIO2): normoxia, hypoxia and hyperoxia. 3. Inert gas levels obtained from blood or expired air samples were sufficient for chromatographic measurement, at least during a 2 h period. The V,A/Q, distributions reported using both methods were acceptable for all the physiological conditions studied; therefore, the alternative method used here may be useful in further MIGET studies in rats because haemodilution resulting from continuous intravenous infusion of less-soluble gases can be avoided. 4. Normoxic rats showed lower mean values of the V,A/Q, ratio of ventilation distribution and higher mean values of the V,A/Q, ratio of perfusion distribution with the usual method of inert gas administration (method A). These non-significant differences were observed under almost all physiological conditions studied and they could be caused by haemodilution. Nevertheless, the effect of interindividual differences cannot be discarded. An additional effect of the low haematocrit on cardiovascular changes due to low FIO2, such as pulmonary vasoconstriction or increased cardiac output, may explain the lower dispersion of perfusion distributions found in group A during hypoxia. [source]