Pressure-induced endothelial Ca(2+) oscillations in lung capillaries |
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Authors: | Kuebler Wolfgang M Ying Xiaoyou Bhattacharya Jahar |
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Institution: | Department of Medicine, College of Physicians and Surgeons, Columbia University, St. Luke's-Roosevelt Hospital Center, New York, New York 10019, USA. |
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Abstract: | 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. |
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