高氧刺激内皮细胞分泌内皮素-1；卡托普利和硝苯地平的调节作用。

Hyperoxia stimulates endothelin-1 secretion from endothelial cells; modulation by captopril and nifedipine.

作者信息

Higgins R D, Hendricks-Munoz K D, Caines V V, Gerrets R P, Rifkin D B

机构信息

Georgetown University Medical Center, Department of Pediatrics, Washington, DC 20007, USA.

出版信息

Curr Eye Res. 1998 May;17(5):487-93. doi: 10.1076/ceyr.17.5.487.5190.

DOI:10.1076/ceyr.17.5.487.5190

PMID:9617543

Abstract

PURPOSE

Retinopathy of prematurity (ROP) is a vasoproliferative condition that can result in severe visual impairment and blindness in preterm babies. Two conditions seen very early in radioimmunoassay (ROP) are vasoconstriction and vaso-obliteration. A potent vasoconstrictor secreted by endothelial cells is endothelin-1 (ET-1). Premature birth results in a relative systemic hyperoxia, compared to the in utero oxygen milieu. We tested the hypothesis that hyperoxia increases ET-1 expression as a possible mechanism for vasoconstriction in the retinal vasculature.

METHODS

Bovine retinal endothelial cells and adrenal capillary endothelial cells were isolated and maintained in culture. Cells were exposed to control or hyperoxic culture conditions for 24 h, with and without addition of captopril and nifedipine. Media was collected and assayed for ET-1 by ROP. In addition, cell counts and secreted LDH assays were performed.

RESULTS

Conditioned media from cultured bovine retinal and adrenal endothelial cells exposed to hyperoxic culture conditions for 24 h were found to have higher levels of ET-1 than conditioned media from normoxic control cells. Captopril (10(-6) M and 10(-4) M) and nifedipine (10(-6) M and 10(-4) M) inhibited ET-1 release from hyperoxia-exposed endothelial cells. Under normoxic conditions, ET-1 release was inhibited by 10(-4) M captopril or 10(-4) M nifedipine.

CONCLUSIONS

These results demonstrate that (1) hyperoxia stimulates in vitro ET-1 secretion in bovine retinal and adrenal capillary endothelial cells, and (2) captopril and nifedipine downregulate ET-1 secretion under normoxic and hyperoxic culture conditions, in a dose-dependent fashion. We speculate that ET-1 may be involved in retinal vessel vasoconstriction seen early in the development of ROP. Further, ACE inhibitors and calcium-channel blocking agents, such as captopril and nifedipine, may provide an avenue for blocking vasoconstriction in ROP.

摘要

目的

早产儿视网膜病变（ROP）是一种血管增殖性疾病，可导致早产婴儿严重视力损害和失明。在ROP早期可见的两种情况是血管收缩和血管闭塞。内皮细胞分泌的一种强效血管收缩剂是内皮素-1（ET-1）。与子宫内的氧环境相比，早产导致相对全身性高氧。我们检验了以下假设：高氧增加ET-1表达，这可能是视网膜血管系统血管收缩的一种机制。

方法

分离牛视网膜内皮细胞和肾上腺毛细血管内皮细胞并进行培养。细胞暴露于对照或高氧培养条件下24小时，添加或不添加卡托普利和硝苯地平。收集培养基并用放射免疫分析法检测ET-1。此外，进行细胞计数和分泌型乳酸脱氢酶检测。

结果

发现暴露于高氧培养条件下24小时的培养牛视网膜和肾上腺内皮细胞的条件培养基中ET-1水平高于常氧对照细胞的条件培养基。卡托普利（10⁻⁶ M和10⁻⁴ M）和硝苯地平（10⁻⁶ M和10⁻⁴ M）抑制高氧暴露的内皮细胞释放ET-1。在常氧条件下，10⁻⁴ M卡托普利或10⁻⁴ M硝苯地平抑制ET-１释放。

结论

这些结果表明：（1）高氧刺激牛视网膜和肾上腺毛细血管内皮细胞体外分泌ET-1；（2）卡托普利和硝苯地平在常氧和高氧培养条件下以剂量依赖方式下调ET-1分泌。我们推测ET-1可能参与ROP发展早期出现的视网膜血管收缩。此外，血管紧张素转换酶抑制剂和钙通道阻滞剂，如卡托普利和硝苯地平，可能为阻断ROP中的血管收缩提供一条途径。