科研之友
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摘要
Endothelial cell Ca2+ signalling is integral to blood flow control in the resistance vasculature yet little is known of how its regulation may be affected by advancing age. We tested the hypothesis that advanced age protects microvascular endothelium by attenuating aberrant Ca2+ signalling during oxidative stress. Intact endothelial tubes (width, similar to 60 mu m; length, similar to 1000 mu m) were isolated from superior epigastric arteries of Young (3-4 months) and Old (24-26 months) male C57BL/6 mice and loaded with Fura-2 dye tomonitor [Ca2+](i). At rest there was no difference in [Ca2+](i) between age groups. Compared to Young, the [Ca2+](i) response to maximal stimulation with acetylcholine (3 mu m, 2 min) was similar to 25% greater in Old, confirming signalling integrity with advanced age. Basal H2O2 availability was similar to 33% greater in Old while vascular catalase activity was reduced by half. Transient exposure to elevated H2O2 (200 mu m, 20 min) progressively increased [Ca2+](i) to similar to 4-fold greater levels in endothelium of Young versus Old. With no difference between age groups at rest, Mn2+ quench of Fura-2 fluorescence revealed 2-fold greater Ca2+ influx in Young during elevated H2O2; this effect was attenuated by similar to 75% using ruthenium red (5 mu m) as a broad-spectrum inhibitor of transient receptor potential channels. Prolonged exposure to H2O2 (200 mu m, 60 min) induced similar to 7-fold greater cell death in endothelium of Young versus Old. Thus, microvascular endothelium can adapt to advanced age by reducing Ca2+ influx during elevated oxidative stress. Protection from cell death during oxidative stress will sustain endothelial integrity during ageing.
- 出版日期2015-5-1
