Pressure-induced endothelial Ca(2+) oscillations in lung capillaries.
Endothelial second messenger responses may contribute to the pathology of high vascular pressure but remain poorly understood because of the lack of direct in situ quantification. In lung venular capillaries, we determined endothelial cytosolic Ca(2+) concentration [Ca(2+)](i) by the fura 2 ratioing method. Pressure elevation increased mean endothelial [Ca(2+)](i) by Ca(2+) influx through gadolinium-inhibitable channels and amplified [Ca(2+)](i) oscillations by Ca(2+) release from intracellular stores. Endothelial [Ca(2+)](i) transients were induced by pressure elevations of as little as 5 cmH(2)O and increased linearly with higher pressures. Heptanol inhibition of [Ca(2+)](i) oscillations in a subset of endothelial cells indicated that oscillations originated from pacemaker endothelial cells and were propagated to adjacent nonpacemaker cells by gap junctional communication. Our findings indicate the presence of a sensitive, active endothelial response to pressure challenge in lung venular capillaries that may be relevant in the pathogenesis of pressure-induced lung microvascular injury.
Kuebler
Wolfgang M
WM
Department of Medicine, College of Physicians and Surgeons, Columbia University, St. Luke's-Roosevelt Hospital Center, New York, New York 10019, USA.
Ying
Xiaoyou
X
Bhattacharya
Jahar
J
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002196:Capillaries / Q000166:cytology / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D005682:Gadolinium / Q000494:pharmacology; D019850:Heptanol / Q000494:pharmacology; D006874:Hydrostatic Pressure; D066298:In Vitro Techniques; D008856:Microscopy, Fluorescence; D011652:Pulmonary Circulation / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000098:blood supply* / Q000502:physiology*; D013314:Stress, Mechanical
D019850:Heptanol; D005682:Gadolinium; D002118:Calcium