Ahn Duck-Sun, Choi Soo-Kyoung, Kim Young-Hwan, Cho Young-Eun, Shin Heung Mook, Morgan Kathleen G, Lee Young-Ho
Department of Physiology, College of Medicine, Yonsei University, Seoul, South Korea.
J Vasc Res. 2007;44(3):182-91. doi: 10.1159/000100374. Epub 2007 Feb 27.
We investigated if the magnitude of myogenic tone in the basilar artery of SHR differs from that in WKY and, if so, whether RhoA- or PKC-dependent mechanisms were involved. Myogenic tone was developed in response to stretch. Stretch-induced myogenic contraction was significantly greater in the SHR than WKY in the presence of external Ca(2+). However, in the absence of external Ca(2+), stretch did not evoke a myogenic tone. The Ca(2+)-induced contraction was larger in SHR than WKY and the Ca(2+)-force curve was significantly shifted to the left in SHR compared to WKY. Y-27632 significantly inhibited stretch-induced myogenic tone, but the inhibitory effect was larger in the SHR than WKY. However, PKC inhibitors had no significant effect on the myogenic tone. RhoA and PKCepsilon were expressed at higher levels in the SHR compared to the WKY. RhoA and PKCalpha translocated from the cytosol to the cell membrane in response to stretch in both animals, but PKCepsilon was translocated only in SHR. Our results strongly suggest that stretch-induced myogenic tone is enhanced in SHR, and the activation of RhoA/Rho kinase plays an important role in the enhanced myogenic tone in SHR.
我们研究了自发性高血压大鼠(SHR)基底动脉的肌源性张力大小是否与WKY大鼠不同,若不同,RhoA或蛋白激酶C(PKC)依赖性机制是否参与其中。肌源性张力是对拉伸的反应而产生的。在存在细胞外Ca(2+)的情况下,拉伸诱导的肌源性收缩在SHR中比WKY大鼠显著更大。然而,在没有细胞外Ca(2+)的情况下,拉伸并未引发肌源性张力。SHR中[Ca(2+)]i诱导的收缩比WKY大鼠更大,并且与WKY大鼠相比,SHR中[Ca(2+)]i-力曲线显著向左移动。Y-27632显著抑制拉伸诱导的肌源性张力,但在SHR中的抑制作用比WKY大鼠更大。然而,PKC抑制剂对肌源性张力没有显著影响。与WKY大鼠相比,SHR中RhoA和PKCε的表达水平更高。在两种动物中,RhoA和PKCα均响应拉伸从细胞质转位到细胞膜,但PKCε仅在SHR中转位。我们的结果强烈表明,SHR中拉伸诱导的肌源性张力增强,并且RhoA/ Rho激酶的激活在SHR增强的肌源性张力中起重要作用。