Côrtes S F, Lemos V S, Stoclet J C
Laboratoire de Pharmacologie et Physiopathologie Cellulaires, Université Louis Pasteur de Strasbourg URA CNRS 600, Faculté de Pharmacie, Illkirch, France.
Hypertension. 1997 Jun;29(6):1322-8. doi: 10.1161/01.hyp.29.6.1322.
The aim of the present work was to further characterize intracellular calcium stores released by angiotensin II (Ang II) in spontaneously hypertensive rat (SHR) and Wistar-Kyoto rat (WKY) vascular smooth muscle cells (VSMCs) and to study their alterations associated with proliferation. Intracellular Ca2+ concentration was monitored by image analysis in aortic myocytes loaded with fura 2. In the presence of extracellular Ca2+, sensitivity to Ang II in proliferating VSMCs was not different in the two strains, but it increased 10-fold in confluent VSMCs from SHR-compared with those from WKY. In Ca(2)+-free medium, Ca2+ release induced by thapsigargin (10 mumol/L) was significantly greater (about twofold) in SHR than WKY, in both proliferating and confluent cultures, with responses during proliferation being 0.7-fold smaller. Responses to Ang II were abolished after exposure of the cells to thapsigargin. In proliferating cultures, ryanodine (10 mumol/L) did not modify the rises in intracellular Ca2+ concentration induced by Ang II in VSMCs from both strains. Conversely, in confluent cultures, ryanodine reduced Ang II (100 nmol/L)-induced Ca2+ release to the same level as in proliferating cultures, and it suppressed the difference between SHR and WKY. These results show that the ryanodine-sensitive Ca2+ release induced by Ang II is enhanced in VSMCs from SHR at confluence and is impaired during proliferation. Thus, they suggest that differences in Ca2+(-)induced Ca2+ release from the sarcoplasmic reticulum may participate in increased responsiveness of VSMCs to Ang II in SHR and in phenotypic modulation of vascular myocytes during proliferation.
本研究的目的是进一步表征血管紧张素II（Ang II）在自发性高血压大鼠（SHR）和Wistar-Kyoto大鼠（WKY）血管平滑肌细胞（VSMC）中释放的细胞内钙库，并研究其与增殖相关的变化。通过图像分析监测加载fura 2的主动脉肌细胞中的细胞内Ca2+浓度。在细胞外Ca2+存在的情况下，两种品系增殖的VSMC对Ang II的敏感性没有差异，但与WKY相比，SHR汇合的VSMC对Ang II的敏感性增加了10倍。在无Ca(2)+的培养基中，无论是增殖培养还是汇合培养，毒胡萝卜素（10 μmol/L）诱导的Ca2+释放，SHR均显著高于WKY（约两倍），增殖期间的反应比WKY小0.7倍。细胞暴露于毒胡萝卜素后，对Ang II的反应消失。在增殖培养中，ryanodine（10 μmol/L）不会改变两种品系VSMC中Ang II诱导的细胞内Ca2+浓度升高。相反，在汇合培养中，ryanodine将Ang II（100 nmol/L）诱导的Ca2+释放降低到与增殖培养相同的水平，并消除了SHR和WKY之间的差异。这些结果表明，Ang II诱导的ryanodine敏感的Ca2+释放在SHR汇合的VSMC中增强，而在增殖期间受损。因此，它们表明肌浆网中Ca2+诱导的Ca2+释放差异可能参与了SHR中VSMC对Ang II反应性的增加以及增殖期间血管平滑肌细胞的表型调节。
