Li Li, Zhang Wen, Shi Wen Yan, Ma Ke-Tao, Zhao Lei, Wang Yang, Zhang Liang, Li Xin-Zhi, Zhu He, Zhang Zhong-Shuang, Liu Wei-Dong, Si Jun-Qiang
Kidney Blood Press Res. 2015;40(1):52-65. doi: 10.1159/000368482.
BACKGROUND/AIMS: This study was designed to investigate the expression and function of gap junction protein connexin 45 (Cx45) in renal interlobar artery (RIA) of spontaneously hypertensive rats (SHR), and the association between hypertension and enhanced vasoconstrictive response in SHR.
Western blot analysis and pressure myography were used to examine the differences in expression and function of Cx45 in vascular smooth muscle cells (VSMCs) of RIA between SHR and normotensive Wistar-Kyoto (WKY) rats.
Our results demonstrated that 1) whole-cell patch clamp measurements showed that the membrane capacitance and conductance of in-situ RIA VSMCs of SHR were significantly greater than those of WKY rats (p<0.05, n=6), suggesting that the coupling of gap junction between VSMCs of RIA was enhanced in SHR; 2) the KCl or phenylephrine (PE)-stimulated RIA constriction was more pronounced in SHR than that in WKY rats (p<0.05, n=10). After applying a gap junction inhibitor 18β-glycyrrhetintic acid (18β-GA), the inhibitory effect of 18β-GA on KCl or PE-induced vasoconstriction was greater in SHR (p<0.05, n=10); and 3) the expression of Cx45 in RIA of SHR was greater than that in WKY rats (p<0.05, n=3) at 4, 12 and 48 wks of age.
The hypertension-induced elevation of Cx45 may affect communication between VSMCs and coupling between VSMCs and endothelium, which results in an increased vasoconstrictive response in renal artery and might contribute to the development of hypertension.
背景/目的：本研究旨在探讨缝隙连接蛋白连接蛋白45（Cx45）在自发性高血压大鼠（SHR）肾叶间动脉（RIA）中的表达及功能，以及高血压与SHR血管收缩反应增强之间的关联。
采用蛋白质免疫印迹分析和压力肌动描记法检测SHR和正常血压的Wistar-Kyoto（WKY）大鼠RIA血管平滑肌细胞（VSMC）中Cx45表达及功能的差异。
我们的结果表明：1）全细胞膜片钳测量显示，SHR原位RIA VSMC的膜电容和电导显著大于WKY大鼠（p<0.05，n=6），提示SHR中RIA的VSMC之间缝隙连接的耦联增强；2）KCl或去氧肾上腺素（PE）刺激下，SHR的RIA收缩比WKY大鼠更明显（p<0.05，n=10）。应用缝隙连接抑制剂18β-甘草次酸（18β-GA）后，18β-GA对KCl或PE诱导的血管收缩的抑制作用在SHR中更强（p<0.05，n=10）；3）在4、12和48周龄时，SHR的RIA中Cx45的表达高于WKY大鼠（p<0.05，n=3）。
高血压诱导的Cx45升高可能影响VSMC之间的通讯以及VSMC与内皮之间的耦联，从而导致肾动脉血管收缩反应增强，并可能促进高血压的发展。
