Effects of Combined Endothelin and Angiotensin II Antagonism on Growth Factor-Induced Proliferation of Vascular Smooth Muscle Cells Isolated from Uremic Rats
Effects of Combined Endothelin and Angiotensin II Antagonism on Growth Factor-Induced Proliferation of Vascular Smooth Muscle Cells Isolated from Uremic Rats
复制标题
内皮素和血管紧张素 II 联合拮抗对生长因子诱导的尿毒症大鼠血管平滑肌细胞增殖的影响
作者：
S. Wolf;G. Sauter;T. Risler;B. Brehm
背景。尿毒症中肾素-血管紧张素-醛固酮和内皮素（ET）系统的激活有助于心血管疾病的发展。因此，ET 受体拮抗剂与血管紧张素转换酶 (ACE) 或血管紧张素 II 1 型 (AT1) 受体抑制剂的组合可以抑制动脉粥样硬化形成。我们研究了不同药物对生长因子诱导的尿毒症大鼠血管平滑肌细胞 (VSMC) 增殖的影响。方法。肾大部切除大鼠（SNX）用ETA受体拮抗剂、氯沙坦、群多普利或ETA受体拮抗剂与氯沙坦或群多普利的组合治疗12周。使用 BrdU-ELISA 测量离体主动脉 SMC 中不同生长因子诱导的增殖。结果。未经治疗的 SNX 中对 PDGF-BB、bFGF 和 TNF-α 的最大增殖反应高于对照组（PDGF-BB：486.60 ± 8.27% 对比 346.74 ± 4.60%，n = 8），在氯沙坦或 ETA 受体拮抗剂单药治疗后减少。群多普利治疗大鼠的 VSMC 对所有生长因子的反应均增强（PDGF-BB：663.48 ± 7.00%，n = 8）。 ETA 受体拮抗剂和群多普利联合治疗后，最大增殖低于未治疗的 SNX（PDGF-BB：162.6 ± 1.40%；n = 8；p ≤ 0.01）。氯沙坦和 ETA 受体拮抗剂联合治疗可最大程度地减弱 PDGF-BB、bFGF 和 TNF 诱导的 VSMC 增殖。结论。与群多普利单一疗法后反应增加相反，SNX 与 ETA 受体拮抗剂和群多普利的联合治疗在体外减少了生长因子诱导的 VSMC 增殖。对尿毒症患者的进一步研究必须阐明内皮素受体拮抗剂和 ACE 抑制剂的组合是否可以抑制动脉粥样硬化形成。
Background. The activation of both the renin–angiotensin–aldosterone and endothelin (ET) system in uremia contributes to the development of cardiovascular disease. The combination of ET receptor antagonists and inhibitors of the angiotensin-converting enzyme (ACE) or angiotensin II type 1 (AT1) receptor could therefore inhibit atherogenesis. We studied the effects of different medications on growth-factor-induced proliferation of vascular smooth muscle cells (VSMC) isolated from uremic rats. Methods. Subtotally nephrectomized rats (SNX) were treated with an ETA receptor antagonist, losartan, trandolapril, or the combinations of an ETA receptor antagonist and losartan or trandolapril for 12 weeks. Proliferation induced by different growth factors in isolated aortal SMC was measured using a BrdU-ELISA. Results. Maximum proliferation in response to PDGF-BB, bFGF, and TNF-α which was higher in untreated SNX than in controls (PDGF-BB: 486.60 ± 8.27% versus 346.74 ± 4.60%, n = 8), was reduced after monotherapy with losartan or the ETA receptor antagonist. VSMC from trandolapril-treated rats showed an increased response to all growth factors (PDGF-BB: 663.48 ± 7.00%, n = 8). After combined therapy with the ETA receptor antagonist and trandolapril, maximum proliferation was lower than in untreated SNX (PDGF-BB: 162.6 ± 1.40%; n = 8; p ≤ 0.01). Combined treatment with losartan and the ETA receptor antagonist attenuated the maximum levels of VSMC proliferation induced by PDGF-BB, bFGF, and TNF. Conclusions. In contrast to an increased response after trandolapril monotherapy, combined treatment of SNX with an ETA receptor antagonist and trandolapril reduced growth-factor-induced VSMC proliferation in vitro. Further investigations in uremic patients have to clarify whether the combination of endothelin receptor antagonists and ACE inhibitors inhibits atherogenesis.
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影响因子：
168.9
作者：
通讯作者：
--
血管平滑肌细胞中缓激肽激活 MAPK 的机制。
DOI：
10.1152/ajpcell.1999.277.2.c253
发表时间：
1999
期刊：
The American journal of physiology
影响因子：
--
作者：
Velarde,V;Ullian,ME;Morinelli,TA;Mayfield,RK;Jaffa,AA
通讯作者：
Jaffa,AA
影响因子：
7.7
作者：
Jaffa, AA;Durazo-Arvizu, R;Schmaier, AH
通讯作者：
Schmaier, AH
影响因子：
158.5
作者：
LEWIS, EJ;HUNSICKER, LG;ROHDE, RD
通讯作者：
ROHDE, RD