title: Pressure is proinflammatory in lung venular capillaries.
abstract: Endothelial responses may contribute importantly to the pathology of high vascular pressure. In lung venular capillaries, we determined endothelial [Ca(2+)](i) by the fura-2 ratioing method and fusion pore formation by quantifying the fluorescence of FM1-43. Pressure elevation increased endothelial [Ca(2+)](i). Concomitantly evoked exocytotic events were evident in a novel spatial-temporal pattern of fusion pore formation. Fusion pores formed predominantly at vascular branch points and colocalized with the expression of P-selectin. Blockade of mechanogated Ca(2+) channels inhibited these responses, identifying entry of external Ca(2+) as the critical triggering mechanism. These endothelial responses point to a proinflammatory effect of high vascular pressure that may be relevant in the pathogenesis of pressure-induced lung disease.
authors.affiliation: Department of Medicine, College of Physicians and Surgeons, Columbia University, St. Luke's-Roosevelt Hospital Center, New York, New York 10019, USA.
authors.forename: W M
authors.initials: WM
authors.lastname: Kuebler
authors.forename: X
authors.initials: X
authors.lastname: Ying
authors.forename: B
authors.initials: B
authors.lastname: Singh
authors.forename: A C
authors.initials: AC
authors.lastname: Issekutz
authors.forename: J
authors.initials: J
authors.lastname: Bhattacharya
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002196:Capillaries / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D007249:Inflammation / Q000209:etiology* / Q000503:physiopathology; D008168:Lung / Q000098:blood supply* / Q000503:physiopathology; D055370:Lung Injury; D008856:Microscopy, Fluorescence; D019007:P-Selectin / Q000378:metabolism; D011652:Pulmonary Circulation / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019007:P-Selectin; D002118:Calcium