Côrtes S F, Lemos V S, Corriu C, Stoclet J C
Laboratoire de Pharmacologie et Physiopathologie Cellulaires, Université Louis Pasteur de Strasbourg, France.
Am J Physiol. 1996 Dec;271(6 Pt 2):H2330-8. doi: 10.1152/ajpheart.1996.271.6.H2330.
The aim of the present work was to characterize angiotensin II (ANG II) receptors and their effect on intracellular free Ca2+ concentration ([Ca2+]i) in proliferating aortic smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Independently from the proliferating state of cultures, apparent affinities of ligands (ANG II > losartan > > CGP-42112A) were consistent with the presence of AT1 receptors in primary cells from SHR and WKY. In proliferating cultures, increases in [Ca2+]i elicited by ANG II (100 nM) were dramatically attenuated or abolished in VSMCs from both strains compared with confluent and postconfluent cultures. Ca2+ releases induced by ionomycin and by ANG II in the absence of extracellular Ca2+ were also impaired in proliferating cultures. In addition, no significant strain difference was found in proliferating cultures with respect to ANG II receptor density, basal [Ca2+]i, and ANG II-induced increases in [Ca2+]i. However, ANG II receptor density significantly increased in SHR, but not in WKY VSMCs at postconfluence. Furthermore, basal [Ca2+]i was elevated in confluent and postconfluent cultures from SHR but not WKY. In confluent cultures, ANG II- and ionomycin-induced Ca2+ releases were enhanced in SHR VSMCs compared with WKY VSMCs. These results show that ANG II-induced Ca2+ release and ionomycin-sensitive Ca2+ stores are enhanced in SHR VSMCs but dramatically decreased in proliferating VSMC cultures from both strains. Mechanisms underlying these alterations remain to be defined. However, the results suggest that alterations in ANG II AT1 receptor density and in intracellular Ca2+ handling in confluent and postconfluent cultures are not associated with the proliferative phenotype of SHR VSMCs. In addition, no evidence for any change in ANG II receptor subtype associated with proliferation of VSMCs was found in either strain.
本研究的目的是表征自发性高血压大鼠（SHR）和正常血压的Wistar-Kyoto大鼠（WKY）增殖的主动脉平滑肌细胞（VSMC）中血管紧张素II（ANG II）受体及其对细胞内游离Ca2+浓度（[Ca2+]i）的影响。与培养物的增殖状态无关，配体的表观亲和力（ANG II > 氯沙坦 > > CGP-42112A）与SHR和WKY原代细胞中AT1受体的存在一致。在增殖培养物中，与汇合和汇合后培养物相比，ANG II（100 nM）引起的两种品系VSMC中[Ca2+]i的增加均显著减弱或消除。在增殖培养物中，离子霉素和在无细胞外Ca2+情况下ANG II诱导的Ca2+释放也受损。此外，在增殖培养物中，关于ANG II受体密度、基础[Ca2+]i以及ANG II诱导的[Ca2+]i增加，未发现品系间有显著差异。然而，汇合后SHR的ANG II受体密度显著增加，而WKY VSMC则未增加。此外，SHR汇合和汇合后培养物中的基础[Ca2+]i升高，而WKY则未升高。在汇合培养物中，与WKY VSMC相比，SHR VSMC中ANG II和离子霉素诱导的Ca2+释放增强。这些结果表明，ANG II诱导的Ca2+释放和离子霉素敏感的Ca2+储存，在SHR VSMC中增强，但在两种品系的增殖VSMC培养物中显著降低。这些改变的潜在机制仍有待确定。然而，结果表明，汇合和汇合后培养物中ANG II AT1受体密度和细胞内Ca2+处理的改变与SHR VSMC增殖表型无关。此外，在两种品系中均未发现与VSMC增殖相关的ANG II受体亚型有任何变化的证据。
