Lack of direct effect of adiponectin on vascular smooth muscle cell BKCa channels or Ca2+ signaling in the regulation of small artery pressure-induced constriction

Lack of direct effect of adiponectin on vascular smooth muscle cell BKCa channels or Ca2+ signaling in the regulation of small artery pressure-induced constriction
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DOI:
10.14814/phy2.13337
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发表时间:
2017-08-01
影响因子:
2.5
通讯作者:
Greenstein, Adam S.
Greenstein, Adam S.
中科院分区:
其他
文献类型:
--
作者:
Baylie, Rachael;Ahmed, Majid;Greenstein, Adam S.

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本研究旨在探讨脂联素影响血管钙信号、钾通道活性从而影响小动脉收缩张力的机制。研究了肠系膜阻力动脉对脂联素的血管扩张作用。用高速共聚焦显微镜对完整动脉的钙信号进行表征。膜片钳研究脂联素对单个VSMC钾通道电流的影响。脂联素扩张的动脉在压力诱导下收缩约5%,诱导的血管扩张只是一过性的。药物阻断钙离子火花/大电导激活的钾(BK)通道通路可降低脂联素的扩张性,但从生理学角度来看,数据的解释受到小效应的限制。脂联素或完整的血管周围脂肪组织(PVAT)的存在都不影响钙火花或钙波的频率或特征。用穿孔贴片方法研究,脂联素略微增加通过VSMC BK通道的电流,但这种作用在细胞质透析的全细胞技术中消失。脂联素不改变钙离子火花诱导的瞬时外向电流的频率和幅度。总体而言,我们的研究表明,脂联素只能引起压力收缩的肠系膜动脉的小幅和一过性扩张。这种血管扩张效应可能不依赖于钙离子火花或BK通道的直接激活。
The aim of this study was to investigate mechanisms by which adiponectin influences vascular Ca2+ signaling, K+ channel activity and thus contractile tone of small arteries. Vasodilation to adiponectin was studied in mesenteric resistance arteries constricted with intraluminal pressure. Ca2+ signals were characterized using high speed confocal microscopy of intact arteries. Patch clamp investigated the effect of adiponectin on individual VSMC potassium (K+) channel currents. Adiponectin dilated arteries constricted with pressure-induced tone by approximately 5% and the induced vasodilation was only transient. The dilation to adiponectin was reduced by pharmacological interruption of the Ca2+ spark/large conductance activated K+ (BK) channel pathway but from a physiological perspective, interpretation of the data was limited by the small effect. Neither Adiponectin nor the presence of intact perivascular adipose tissue (PVAT) influenced Ca2+ spark or Ca2+ wave frequency or characteristics. Studied using a perforated patch approach, Adiponectin marginally increased current through the VSMC BK channel but this effect was lost using the whole cell technique with dialysis of the cytoplasm. Adiponectin did not change the frequency or amplitude of Ca2+ spark-induced transient outward currents (STOC). Overall, our study shows that Adiponectin induces only a small and transient dilation of pressure constricted mesenteric arteries. This vasodilatory effect is likely to be independent of Ca2+ sparks or direct BK channel activation.