			Home About us Contact

Hypoxic Pulmonary Vasoconstriction (hypoxic + pulmonary_vasoconstriction)

Distribution by Scientific Domains

Medical Sciences	60%

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]

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]

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