Hendricks-Munoz K D, Gerrets R P, Higgins R D, Munoz J L, Caines V V
Neonatal Program, Department of Pediatrics, New York University Medical Center, NY 10016, USA.
Cardiovasc Res. 1996 Jan;31(1):117-23. doi: 10.1016/s0008-6363(95)00168-9.
The primary aim was to determine the action of pathophysiologically relevant cocaine concentrations (10(-7)-10(-5) M) on endothelin-1 (ET-1) release from cultured endothelial cells under various cellular conditions. Further aims were to evaluate the effect of angiotensin-converting enzyme inhibitors on cocaine-treated endothelial cells, to assess their potential for inhibition of ET-1-stimulated release.
Endothelin-1 release into the media was evaluated by radioimmunoassay under basal conditions and after 24 h treatment of endothelial cells with cocaine hydrochloride (HCl), or cocaine HCl and ACE inhibitors, captopril and lisinopril. The effect of serum and plasma under these conditions was also investigated.
Cocaine HCl stimulated ET-1 release in a dose response fashion that was independent of plasma or serum factors. Furthermore, cocaine-stimulated ET-1 release was inhibited by administration of angiotensin-converting enzyme inhibitors captopril and lisinopril.
These findings suggest that cocaine can directly stimulate endothelial cells to release ET-1 and that the observed increase is independent of serum or plasma factors. Furthermore, cocaine-stimulated endothelin-1 release appears to be mediated at least in part by the angiotensin system. These observations provide a framework for understanding the cellular mechanisms involved in cocaine-induced vasoconstriction.
主要目的是确定病理生理相关浓度的可卡因（10⁻⁷ - 10⁻⁵ M）在不同细胞条件下对培养的内皮细胞释放内皮素-1（ET-1）的作用。进一步的目的是评估血管紧张素转换酶抑制剂对可卡因处理的内皮细胞的影响，以评估其抑制ET-1刺激释放的潜力。
通过放射免疫分析法在基础条件下以及用盐酸可卡因（HCl）或盐酸可卡因与血管紧张素转换酶抑制剂卡托普利和赖诺普利处理内皮细胞24小时后，评估培养基中内皮素-1的释放情况。还研究了这些条件下血清和血浆的影响。
盐酸可卡因以剂量反应方式刺激ET-1释放，且与血浆或血清因子无关。此外，血管紧张素转换酶抑制剂卡托普利和赖诺普利可抑制可卡因刺激的ET-1释放。
这些发现表明，可卡因可直接刺激内皮细胞释放ET-1，且观察到的增加与血清或血浆因子无关。此外，可卡因刺激的内皮素-1释放似乎至少部分由血管紧张素系统介导。这些观察结果为理解可卡因诱导血管收缩所涉及的细胞机制提供了一个框架。
