Angiotensin-(1-7) inhibits vascular smooth muscle cell growth
Angiotensin-(1-7) inhibits vascular smooth muscle cell growth
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DOI：
10.1161/01.hyp.28.1.104
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发表时间：
1996-07-01
期刊：
影响因子：
8.3
通讯作者：
Tallant, EA
中科院分区：
文献类型：
--
作者：
Freeman, EJ;Chisolm, GM;Tallant, EA
虽然血管紧张素II(Ang II)和七肽Ang-(1-7)只有一个氨基酸的差异，但这两个肽在血管平滑肌细胞上产生不同的反应。我们先前的研究表明，Ang II刺激肌醇磷脂的水解，而Ang II和Ang-(1-7)则释放前列腺素。我们现在报道Ang II和Ang-(1-7)对大鼠主动脉血管平滑肌细胞生长的不同调节作用。血管紧张素-(1-7)抑制胎牛血清、血小板衍生生长因子或血管紧张素Ⅱ刺激的[H-3]胸腺嘧啶核苷掺入。血管紧张素-(1-7)对血清刺激的胸腺嘧啶核苷掺入的抑制作用在1nmol/L~1mU/L范围内依赖于七肽的浓度，1mU/L对胸腺嘧啶核苷掺入的最大抑制率为60%。Ang-(1-7)还可抑制1mU·mol/L所致的血清刺激的细胞数增加，最高可达77%。血管紧张素1型(ATI)和2型(AT(2))受体拮抗剂不影响Ang-(1-7)对血清刺激的胸腺嘧啶核苷掺入的抑制作用，但[Sar(1)，Ile(8)]Ang II和[Sar(1)，Thr(8)]Ang II是有效的拮抗剂，提示Ang-(1-7)的生长抑制是血管紧张素受体激活的结果。相反，血管紧张素Ⅱ在相同浓度范围内刺激培养的血管平滑肌细胞[H-3]胸腺嘧啶核苷掺入，在1mU/L浓度时刺激作用最大，达314%。血管紧张素Ⅱ还使细胞总数增加(为对照的145%)，提示胸腺嘧啶核苷掺入增加与血管平滑肌细胞增殖有关。血管紧张素转换酶抑制剂氯沙坦或L-158,809但不能阻断血管紧张素转换酶II对[H-3]胸腺嘧啶核苷的掺入。这些结果表明，血管紧张素转换酶抑制剂1-7和血管紧张素转换酶1对血管平滑肌细胞的生长具有相反的调节作用。Ang-(1-7)对细胞增殖的抑制作用可能是通过一种新的血管紧张素受体介导的，该受体不受AT(1)或AT(2)受体拮抗剂的抑制。
Although angiotensin II (Ang II) and the heptapeptide Ang-(1-7) differ by only one amino acid, the two peptides produce different responses in vascular smooth muscle cells. We previously showed that Ang II stimulated phosphoinositide hydrolysis, whereas Ang II and Ang-(1-7) released prostaglandins. We now report that Ang II and Ang-(1-7) differentially modulate rat aortic vascular smooth muscle cell growth. Ang-(1-7) inhibited [H-3]thymidine incorporation in response to stimulation by fetal bovine serum, platelet-derived growth factor, or Ang Ii, The reduction in serum-stimulated thymidine incorporation by Ang-(1-7) depended on the concentration of the heptapeptide over the range of 1 nmol/L, to 1 mu mol/L, with a maximal inhibition of 60% by 1 mu mol/L Ang-(1-7). Ang-(1-7) also inhibited the serum-stimulated increase in cell number to a maximum of 77% by 1 mu mol/L, Ang-(1-7). The attenuation of serum-stimulated thymidine incorporation by Ang-(1-7) was unaffected by antagonists selective for angiotensin type 1 (ATI) or type 2 (AT(2)) receptors; however, [Sar(1),Ile(8)]Ang II and [Sar(1),Thr(8)]Ang II were effective antagonists, indicating that growth inhibition by Ang-(1-7) was a result of angiotensin receptor activation. In contrast, Ang II stimulated [H-3]thymidine incorporation in cultured vascular smooth muscle cells over the same concentration range, with a maximal stimulation of 314% at I mu mol/L Ang II. Ang II also increased the total number of cells (to 145% of control), suggesting that enhanced thymidine incorporation was associated with vascular smooth muscle cell proliferation. The ATI antagonist losartan or L-158,809 but not AT(2) antagonists blocked [H-3]thymidine incorporation by Ang II. These results suggest that Ang-(1-7) and Ang Il exhibit opposite effects on the regulation of vascular smooth muscle cell growth. The inhibition of proliferation by Ang-(1-7) appears to be mediated by a novel angiotensin receptor that is not inhibited by AT(1) or AT(2) receptor antagonists.