Segmental regulation of pulmonary vascular permeability by store-operated Ca2+ entry.
An intact endothelial cell barrier maintains normal gas exchange in the lung, and inflammatory conditions result in barrier disruption that produces life-threatening hypoxemia. Activation of store-operated Ca2+ (SOC) entry increases the capillary filtration coefficient (Kf,c) in the isolated rat lung; however, activation of SOC entry does not promote permeability in cultured rat pulmonary microvascular endothelial cells. Therefore, current studies tested whether activation of SOC entry increases macro- and/or microvascular permeability in the intact rat lung circulation. Activation of SOC entry by the administration of thapsigargin induced perivascular edema in pre- and postcapillary vessels, with apparent sparing of the microcirculation as evaluated by light microscopy. Scanning and transmission electron microscopy revealed that the leak was due to gaps in vessels >/= 100 micrometer, consistent with the idea that activation of SOC entry influences macrovascular but not microvascular endothelial cell shape. In contrast, ischemia and reperfusion induced microvascular endothelial cell disruption independent of Ca2+ entry, which similarly increased Kf,c. These data suggest that 1) activation of SOC entry is sufficient to promote macrovascular barrier disruption and 2) unique mechanisms regulate pulmonary micro- and macrovascular endothelial barrier functions.
Chetham
P M
PM
Department of Anesthesiology and Cardiovascular-Pulmonary Research Laboratory, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Babál
P
P
Bridges
J P
JP
Moore
T M
TM
Stevens
T
T
D000818:Animals; D001808:Blood Vessels / Q000648:ultrastructure; D001980:Bronchi / Q000098:blood supply; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D066298:In Vitro Techniques; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology; D008168:Lung / Q000473:pathology; D008297:Male; D008833:Microcirculation / Q000502:physiology; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology; D019284:Thapsigargin / Q000494:pharmacology
D019284:Thapsigargin; D002118:Calcium