To investigate the possible cellular mechanisms of the ischemia-induced impairments of cerebral microcirculation, we investigated the effects of hypoxia/reoxygenation on the intracellular Ca2+ concentration ([Ca2+](i)) in bovine brain microvascular endothelial cells (BBEC). In the cells kept in normal air, ATP elicited Ca2+ oscillations in a concentration-dependent manner. When the cells were exposed to hypoxia for 6 h and subsequent reoxygenation for 45 min, the basal level of [Ca2+](i) was increased from 32.4 to 63.3 nM, and ATP did not induce Ca2+ oscillations. Hypoxia/reoxygenation also inhibited capacitative Ca2+ entry (CCE), which was evoked by thapsigargin (Δ[Ca2+](i-CCE): control, 62.3 ± 3.1 nM; hypoxia/ reoxygenation, 17.0 ± 1.8 nM). The impairments of Ca2+ oscillations and CCE, but not basal [Ca2+](i), were restored by superoxide dismutase and the inhibitors of mitochondrial electron transport, rotenone and thenoyltrifluoroacetone (TTFA). By using a superoxide anion (O2/-)-sensitive luciferin derivative MCLA, we confirmed that the production of O2/- was induced by hypoxia/reoxygenation and was prevented by rotenone and TTFA. These results indicate that hypoxia/ reoxygenation generates O2/- at mitochondria and impairs some Ca2+ mobilizing properties in BBEC.
|Journal||American Journal of Physiology - Heart and Circulatory Physiology|
|Issue number||5 48-5|
|Publication status||Published - 2000|
All Science Journal Classification (ASJC) codes
- Cardiology and Cardiovascular Medicine
- Physiology (medical)