{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T14:05:15Z","timestamp":1765807515310},"reference-count":32,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Applied Physiology"],"published-print":{"date-parts":[[2001,6,1]]},"abstract":"<jats:p>The hydrogen ion is an important factor in the alteration of vascular tone in pulmonary circulation. Endothelial cells modulate vascular tone by producing vasoactive substances such as prostacyclin (PGI<jats:sub>2<\/jats:sub>) through a process depending on intracellular Ca<jats:sup>2+<\/jats:sup>concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>). We studied the influence of CO<jats:sub>2<\/jats:sub>-related pH changes on [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>and PGI<jats:sub>2<\/jats:sub>production in human pulmonary artery endothelial cells (HPAECs). Hypercapnic acidosis appreciably increased [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>from 112 \u00b1 24 to 157 \u00b1 38 nmol\/l. Intracellular acidification at a normal extracellular pH increased [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>comparable to that observed during hypercapnic acidosis. The hypercapnia-induced increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>was unchanged by the removal of Ca<jats:sup>2+<\/jats:sup>from the extracellular medium or by the depletion of thapsigargin-sensitive intracellular Ca<jats:sup>2+<\/jats:sup>stores. Hypercapnic acidosis may thus release Ca<jats:sup>2+<\/jats:sup>from pH-sensitive but thapsigargin-insensitive intracellular Ca<jats:sup>2+<\/jats:sup>stores. Hypocapnic alkalosis caused a fivefold increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>compared with hypercapnic acidosis. Intracellular alkalinization at a normal extracellular pH did not affect [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>. The hypocapnia-evoked increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>was decreased from 242 \u00b1 56 to 50 \u00b1 32 nmol\/l by the removal of extracellular Ca<jats:sup>2+<\/jats:sup>. The main mechanism affecting the hypocapnia-dependent [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>increase was thought to be the augmented influx of extracellular Ca<jats:sup>2+<\/jats:sup>mediated by extracellular alkalosis. Hypercapnic acidosis caused little change in PGI<jats:sub>2<\/jats:sub>production, but hypocapnic alkalosis increased it markedly. In conclusion, both hypercapnic acidosis and hypocapnic alkalosis increase [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>in HPAECs, but the mechanisms and pathophysiological significance of these increases may differ qualitatively.<\/jats:p>","DOI":"10.1152\/jappl.2001.90.6.2094","type":"journal-article","created":{"date-parts":[[2017,12,22]],"date-time":"2017-12-22T21:38:33Z","timestamp":1513978713000},"page":"2094-2100","source":"Crossref","is-referenced-by-count":19,"title":["Effects of hypercapnia and hypocapnia on [Ca<sup>2+<\/sup>]<sub>i<\/sub>mobilization in human pulmonary artery endothelial cells"],"prefix":"10.1152","volume":"90","author":[{"given":"Kazumi","family":"Nishio","sequence":"first","affiliation":[{"name":"Department of Medicine, Kitasato Institute Hospital, Tokyo 108-8642, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukio","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Medicine, Kitasato Institute Hospital, Tokyo 108-8642, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kei","family":"Takeshita","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, Keio University, Tokyo 160-8582; 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