Effects of hypercapnia and hypocapnia on [Ca2+]i mobilization in human pulmonary artery endothelial cells.
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.
Nishio
K
K
Department of Medicine, Kitasato Institute Hospital, Tokyo 108-8642, Japan.
Suzuki
Y
Y
Takeshita
K
K
Aoki
T
T
Kudo
H
H
Sato
N
N
Naoki
K
K
Miyao
N
N
Ishii
M
M
Yamaguchi
K
K
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
D005452:Fluoresceins; D005456:Fluorescent Dyes; D014280:Triglycerides; C043829:2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein; D011464:Epoprostenol; D002118:Calcium; D016257:Fura-2