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 produ cing vasoactive substances such as prostacyclin (PGI(2)) through a process depending on intracellular Ca2+ concentration ([Ca2+](i)). We studied the i nfluence of CO2-related pH changes on [Ca2+](i) and PGI(2) production in hu man pulmonary artery endothelial cells (HPAECs). Hypercapnic acidosis appre ciably increased [Ca2+](i) from 112 +/- 24 to 157 +/- 38 nmol/l. Intracellu lar acidification at a normal extracellular pH increased [Ca2+](i) comparab le to that observed during hypercapnic acidosis. The hypercapnia-induced in crease in [Ca2+](i) was unchanged by the removal of Ca2+ from the extracell ular 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 ca used a fivefold increase in [Ca2+](i) compared with hypercapnic acidosis. I ntracellular alkalinization at a normal extracellular pH did not affect [Ca 2+](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 m echanism 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 PGI(2) production, but hypocapnic alkalosis increased it markedly. In conclusion, both hyperca pnic acidosis and hypocapnic alkalosis increase [Ca2+](i) in HPAECs, but th e mechanisms and pathophysiological significance of these increases may dif fer qualitatively.