Erratum: Endothelin-1-Mediated Wave-Like [Ca2+]i Oscillations in Intact Rabbit Inferior Vena Cava

Endothelin-1 (ET1) is an endogenous vasoconstrictor released by the vascular system to regulate the contractility of vascular smooth muscle cells (VSMC). It is implicated in the pathogenesis of hypertension and diabetic vasculopathy. In rabbit inferior vena cava (IVC), 10 nM ET1 induces tonic contraction mainly via type A endothelin receptor activation. Using confocal imaging of Fluo-3 loaded in thein situ VSMC within the intact IVC, we found that ET1 elicited [Ca2+]i oscillations with an average frequency of 0.31 ± 0.01 Hz. These [Ca2+]i oscillations occurred as repetitive Ca2+ waves traveling along the longitudinal axis of the cells with an average velocity of 29 ± 3 µm/s. The Ca2+ waves were not synchronized between neighboring VSMC nor were they propagated between them. Nifedipine (10 µM) inhibited the tonic contraction by 27.0 ± 5.0% while SKF96365 (50 µM) abolished the remaining contraction. In a parallel Ca2+ study, nifedipine reduced the frequency of the oscillations to 0.22 ± 0.01 Hz while SKF96365 abolished the remaining [Ca2+]i oscillations. Subsequent application of 25 mM caffeine elicited no further Ca2+ signal. Thus, we conclude that ET1 stimulates tonic contraction in the rabbit IVC by inducing [Ca2+]i oscillations and that stimulated Ca2+ entry through both the L-type voltage-gated Ca2+ channels and a nifedipine-resistant and SKF96365-sensitive pathway is crucial for the maintenance of [Ca2+]i oscillations and tonic contraction.

内皮素-1（Endothelin-1, ET1）是由血管系统释放的内源性血管收缩剂，用于调节血管平滑肌细胞（vascular smooth muscle cells, VSMC）的收缩活性，其与高血压及糖尿病性血管病变的发病机制密切相关。在兔下腔静脉（rabbit inferior vena cava, IVC）中，10 nM的ET1主要通过激活A型内皮素受体诱导张力性收缩。本研究通过对完整IVC内原位加载Fluo-3荧光探针的VSMC进行共聚焦成像，发现ET1可诱发细胞内钙离子浓度（intracellular calcium concentration, [Ca²⁺]i）振荡，平均频率为0.31 ± 0.01 Hz。此类[Ca²⁺]i振荡表现为沿细胞纵轴传播的重复性钙波，平均传播速度为29 ± 3 µm/s。相邻VSMC间的钙波既不同步，也无法在细胞间传递。硝苯地平（Nifedipine, 10 µM）可抑制27.0 ± 5.0%的张力性收缩，而SKF96365（50 µM）则可完全抑制剩余的收缩反应。在平行开展的钙离子实验中，硝苯地平可将振荡频率降至0.22 ± 0.01 Hz，而SKF96365则可完全消除剩余的[Ca²⁺]i振荡。后续加入25 mM咖啡因未再引发额外的钙信号。综上，本研究认为ET1通过诱发[Ca²⁺]i振荡介导兔IVC的张力性收缩；且通过L型电压门控钙离子通道、以及硝苯地平抵抗但SKF96365敏感的通路介导的钙离子内流，对于维持[Ca²⁺]i振荡与张力性收缩至关重要。