title: Effects of hypercapnia and hypocapnia on [Ca2+]i mobilization in human pulmonary artery endothelial cells.
abstract: 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 (PGI2) through a process depending on intracellular Ca2+ concentration ([Ca2+]i). We studied the influence of CO2-related pH changes on [Ca2+]i and PGI2 production in human pulmonary artery endothelial cells (HPAECs). Hypercapnic acidosis appreciably increased [Ca2+]i from 112 +/- 24 to 157 +/- 38 nmol/l. Intracellular acidification at a normal extracellular pH increased [Ca2+]i comparable to that observed during hypercapnic acidosis. The hypercapnia-induced increase in [Ca2+]i was unchanged by the removal of Ca2+ from the extracellular medium or by the depletion of thapsigargin-sensitive intracellular Ca2+ stores. Hypercapnic acidosis may thus release Ca2+ from pH-sensitive but thapsigargin-insensitive intracellular Ca2+ stores. Hypocapnic alkalosis caused a fivefold increase in [Ca2+]i compared with hypercapnic acidosis. Intracellular alkalinization at a normal extracellular pH did not affect [Ca2+]i. The hypocapnia-evoked increase in [Ca2+]i was decreased from 242 +/- 56 to 50 +/- 32 nmol/l by the removal of extracellular Ca2+. The main mechanism affecting the hypocapnia-dependent [Ca2+]i increase was thought to be the augmented influx of extracellular Ca2+ mediated by extracellular alkalosis. Hypercapnic acidosis caused little change in PGI2 production, but hypocapnic alkalosis increased it markedly. In conclusion, both hypercapnic acidosis and hypocapnic alkalosis increase [Ca2+]i in HPAECs, but the mechanisms and pathophysiological significance of these increases may differ qualitatively.
authors.affiliation: Department of Medicine, Kitasato Institute Hospital, Tokyo 108-8642, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nishio
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Takeshita
authors.forename: T
authors.initials: T
authors.lastname: Aoki
authors.forename: H
authors.initials: H
authors.lastname: Kudo
authors.forename: N
authors.initials: N
authors.lastname: Sato
authors.forename: K
authors.initials: K
authors.lastname: Naoki
authors.forename: N
authors.initials: N
authors.lastname: Miyao
authors.forename: M
authors.initials: M
authors.lastname: Ishii
authors.forename: K
authors.initials: K
authors.lastname: Yamaguchi
mesh_terms: D000142:Acidosis, Respiratory / Q000378:metabolism; D000472:Alkalosis, Respiratory / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis; D005110:Extracellular Space / Q000378:metabolism; D005452:Fluoresceins; D005456:Fluorescent Dyes; D016257:Fura-2; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006935:Hypercapnia / Q000378:metabolism*; D016857:Hypocapnia / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology* / Q000378:metabolism*; D014280:Triglycerides / Q000502:physiology
chemical_list: D005452:Fluoresceins; D005456:Fluorescent Dyes; D014280:Triglycerides; C043829:2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein; D011464:Epoprostenol; D002118:Calcium; D016257:Fura-2