In the lung, chronic hypoxia (CH) causes pulmonary arterial smooth muscle cell (PASMC) depolarization, elevated endothelin-1 (ET-1), and vasoconstriction. We determined whether, during CH, depolarization-driven activation of L-type Ca2+ channels contributes to 1) maintenance of resting intracellular Ca2+ concentration ([Ca2+]i), 2) increased [Ca2+]i in response to ET-1 (10−8 M), and 3) ET-1-induced contraction. Using indo 1 microfluorescence, we determined that resting [Ca2+]i in PASMCs from intrapulmonary arteries of rats exposed to 10% O2 for 21 days was 293.9 ± 25.2 nM (vs. 153.6 ± 28.7 nM in normoxia). Resting [Ca2+]i was decreased after extracellular Ca2+ removal but not with nifedipine (10−6 M), an L-type Ca2+ channel antagonist. After CH, the ET-1-induced increase in [Ca2+]i was reduced and was abolished after extracellular Ca2+ removal or nifedipine. Removal of extracellular Ca2+ reduced ET-1-induced tension; however, nifedipine had only a slight effect. These data indicate that maintenance of resting [Ca2+]i in PASMCs from chronically hypoxic rats does not require activation of L-type Ca2+ channels and suggest that ET-1-induced contraction occurs by a mechanism primarily independent of changes in [Ca2+]i.
Role of Na
+
/Ca
2+
exchange in maintenance of elevated pulmonary arterial smooth muscle cell (PASMC) intracellular Ca
2+
concentration ([Ca
2+
]
i
) and intracellular pH (pHi) during chronic hypoxia (CH)
