Role of gap junctions in the contractile response to agonists in the mesenteric artery of spontaneously hypertensive rats
Role of gap junctions in the contractile response to agonists in the mesenteric artery of spontaneously hypertensive rats
复制标题
间隙连接在自发性高血压大鼠肠系膜动脉激动剂收缩反应中的作用
DOI：
10.1038/hr.2013.120
复制
发表时间：
2014-02-01
影响因子：
5.4
通讯作者：
Si, Jun-Qiang
中科院分区：
文献类型：
--
作者：
Ma, Ke-Tao;Li, Xin-Zhi;Si, Jun-Qiang
目的：探讨高血压对自发性高血压大鼠(SHR)肠系膜动脉(MA)血管平滑肌细胞(VSMCs)缝隙连接的影响。采用全细胞膜片钳、压力肌图、实时定量逆转录聚合酶链式反应(qRT-PCR)、免疫印迹分析和透射电子显微镜等方法，观察SHR和正常血压WKY大鼠MA VSMCs缝隙连接的表达和功能的差异：(1)SHR大鼠原位MA VSMCs膜电容和电导显著高于WKY大鼠(P<；(2)苯肾上腺素(PE)和KCl(一种非内皮依赖的血管收缩药)对SHR大鼠的血管收缩作用较WKY大鼠更为明显(P<；0.05)。此外，缝隙连接抑制剂2-APB可减弱PE和KCl引起的血管收缩，且2-APB的抑制作用在SHR显著增强(P<；0.05)。(3)SHR大鼠MA中连接蛋白45(Cx45)的表达高于WKY大鼠(P<；0.05)。与WKY大鼠相比，SHR大鼠MA中Cx43的磷酸化水平显著升高(P<；0.05)，而MA中Cx43的总mRNA和蛋白表达与SHR和WKY大鼠相当。电子显微镜显示SHR大鼠的缝隙连接明显大于WKY大鼠。Cx45表达的增加和Cx43的磷酸化可能有助于增强SHR MA VSMCs之间的缝隙连接通讯，从而增强对激动剂的收缩反应。
To investigate the effects of hypertension on the changes in gap junctions between vascular smooth muscle cells (VSMCs) in the mesenteric artery (MA) of spontaneously hypertensive rats (SHRs). Whole-cell patch clamp, pressure myography, real-time quantitative reverse transcription PCR (qRT-PCR), western blot analysis and transmission electron microscopy were used to examine the differences in expression and function of the gap junction between MA VSMCs of SHR and control normotensive Wistar-Kyoto (WKY) rats.(1) Whole-cell patch clamp measurements showed that the membrane capacitance and conductance of in-situ MA VSMCs of SHR were significantly greater than those of WKY rats (P< 0.05), suggesting enhanced gap junction coupling between MA VSMCs of SHR.(2) The administration of phenylephrine (PE) and KCl (an endothelium-independent vasoconstrictor) initiated more pronounced vasoconstriction in SHR versus WKY rats (P< 0.05). Furthermore, 2-APB (a gap junction inhibitor) attenuated PE-and KCl-induced vasoconstriction, and the inhibitory effects of 2-APB were significantly greater in SHR (P< 0.05).(3) The expression of connexin 45 (Cx45) mRNA and protein in the MA was greater in SHR versus WKY rats (P< 0.05). The level of phosphorylated Cx43 was significantly higher in SHR versus WKY rats (P< 0.05), although the expression of total Cx43 mRNA and protein in the MA was equivalent between SHR and WKY rats. Electron microscopy revealed that the gap junctions were significantly larger in SHR versus WKY rats. Increases in the expression of Cx45 and phosphorylation of Cx43 may contribute to the enhancement of communication across gap junctions between MA VSMCs of SHR, which may increase the contractile response to agonists.