Hu W Y, Fukuda N, Soma M, Izumi Y, Kanmatsuse K
Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
J Cardiovasc Pharmacol. 1998 Dec;32(6):975-82. doi: 10.1097/00005344-199812000-00015.
Selective alpha1-adrenoreceptor blockers were recently reported to have an in vivo antiproliferative effect on hypertensive cardiovascular organs. Cultured vascular smooth-muscle cells (VSMCs) from spontaneously hypertensive rats (SHRs) show exaggerated growth compared with cells from Wistar-Kyoto (WKY) rats. We investigated the effects of an alpha1-adrenoreceptor blocker, bunazosin hydrochloride (HCl), on the growth of VSMCs from SHRs. In the absence of serum, bunazosin HCl significantly inhibited basal DNA synthesis by VSMCs from SHRs, but not by cells from WKY rats. In the presence of serum, bunazosin HCl significantly inhibited DNA synthesis by VSMCs from both rat strains. Angiotensin (Ang) II, platelet-derived growth factor (PDGF)-AA, and epidermal growth factor (EGF) dose-dependently increased DNA synthesis by VSMCs from SHRs, but not by VSMCs from WKY rats. Bunazosin HCl significantly suppressed the response of DNA synthesis to PDGF-AA and EGF, but not to Ang II, in VSMCs from SHRs. Expression of basic fibroblast growth factor (bFGF), transforming growth factor-beta1 (TGFbeta1), and PDGF messenger RNA (mRNA) was markedly greater in VSMCs from SHRs than in cells from WKY rats. Bunazosin HCl significantly inhibited the expression of bFGF and TGFbeta1 mRNA in VSMCs from SHRs, but not in cells from WKY rats. These findings suggest that the inhibition of growth factor hyperresponsiveness and inhibition of the expression of growth factors in VSMCs from SHRs are associated with the antiproliferative effect of bunazosin.
最近有报道称，选择性α1-肾上腺素能受体阻滞剂对高血压心血管器官具有体内抗增殖作用。与来自Wistar-Kyoto（WKY）大鼠的血管平滑肌细胞（VSMC）相比，自发性高血压大鼠（SHR）的培养VSMC显示出过度生长。我们研究了α1-肾上腺素能受体阻滞剂盐酸布那唑嗪对SHR来源的VSMC生长的影响。在无血清条件下，盐酸布那唑嗪显著抑制SHR来源的VSMC的基础DNA合成，但对WKY大鼠来源的细胞无此作用。在有血清的情况下，盐酸布那唑嗪显著抑制两种大鼠品系来源的VSMC的DNA合成。血管紧张素（Ang）II、血小板衍生生长因子（PDGF）-AA和表皮生长因子（EGF）剂量依赖性地增加SHR来源的VSMC的DNA合成，但对WKY大鼠来源的VSMC无此作用。盐酸布那唑嗪显著抑制SHR来源的VSMC对PDGF-AA和EGF的DNA合成反应，但对Ang II无此作用。碱性成纤维细胞生长因子（bFGF）、转化生长因子-β1（TGFβ1）和PDGF信使核糖核酸（mRNA）在SHR来源的VSMC中的表达明显高于WKY大鼠来源的细胞。盐酸布那唑嗪显著抑制SHR来源的VSMC中bFGF和TGFβ1 mRNA的表达，但对WKY大鼠来源的细胞无此作用。这些发现表明，抑制SHR来源的VSMC中生长因子的高反应性以及生长因子的表达与布那唑嗪的抗增殖作用有关。
