CAPTOPRIL INHIBITS ENDOTHELIN-1 SECRETION FROM ENDOTHELIAL-CELLS THROUGH BRADYKININ
CAPTOPRIL INHIBITS ENDOTHELIN-1 SECRETION FROM ENDOTHELIAL-CELLS THROUGH BRADYKININ
复制标题
DOI：
10.1161/01.hyp.21.6.921
复制
发表时间：
1993-06-01
期刊：
影响因子：
8.3
通讯作者：
OGIHARA, T
中科院分区：
文献类型：
--
作者：
MOMOSE, N;FUKUO, K;OGIHARA, T
与卡托普利（一种血管紧张素I转换酶抑制剂）一起孵育24小时，浓度高达10(-7) M，可抑制内皮细胞分泌内皮素-1。通过与一氧化氮合成抑制剂 3 x 10(-3) M N(G)-硝基-L-精氨酸共孵育可逆转内皮素-1 分泌的抑制作用。此外，卡托普利增强内皮细胞中一氧化氮的产生，表明一氧化氮产生的增强参与卡托普利诱导的内皮素-I分泌抑制。此外，在存在 10(-6) M D-Arg,[Hyp3,Thi5,8,D-Phe7]-缓激肽（一种缓激肽 B2 受体拮抗剂）的情况下，卡托普利不会抑制而是刺激内皮素-1 分泌，而缓激肽则抑制内皮素-1 分泌，并且通过与 N(G)-硝基-L-精氨酸共孵育可逆转缓激肽的这种抑制作用。此外，由卡托普利或缓激肽诱导的一氧化氮生成的增强被 D-Arg,[Hyp3,Thi5,8,D-Phe7]-缓激肽抑制。尽管10(-6) M des-Arg9-[Leu8]-缓激肽（一种缓激肽B1受体拮抗剂）不影响缓激肽产生一氧化氮，但它增强了缓激肽对内皮素-I分泌的抑制。此外，10(-7) M des-Arg9-缓激肽（一种缓激肽B1受体激动剂）可刺激内皮细胞分泌内皮素-1。这些发现表明，血管紧张素I转换酶抑制剂通过内皮细胞中内源性缓激肽的积累来抑制内皮素-I的分泌，并且缓激肽对内皮素-I分泌的抑制是通过B2受体介导的。
Incubation with captopril, an angiotensin I converting enzyme inhibitor, for 24 hours at concentrations up to 10(-7) M inhibited endothelin-1 secretion by endothelial cells. This inhibition of endothelin-1 secretion was reversed by coincubation with 3 x 10(-3) M N(G)-nitro-L-arginine, an inhibitor of nitric oxide synthesis. Furthermore, captopril enhanced the production of nitric oxide in endothelial cells, suggesting that enhancement of nitric oxide production participates in captopril-induced inhibition of endothelin-I secretion. Moreover, in the presence of 10(-6) M D-Arg,[Hyp3,Thi5,8,D-Phe7]-bradykinin, a bradykinin B2 receptor antagonist, captopril did not inhibit but rather stimulated endothelin-1 secretion, whereas bradykinin inhibited endothelin-1 secretion, and this inhibition by bradykinin was reversed by coincubation with N(G)-nitro-L-arginine. In addition, enhancement of nitric oxide production induced by either captopril or bradykinin was inhibited by D-Arg,[Hyp3,Thi5,8,D-Phe7]-bradykinin. Although 10(-6) M des-Arg9-[Leu8]-bradykinin, a bradykinin B1 receptor antagonist, did not affect nitric oxide production by bradykinin, it enhanced the inhibition of endothelin-I secretion by bradykinin. Furthermore, 10(-7) M des-Arg9-bradykinin, a bradykinin B1 receptor agonist, stimulated endothelin-1 secretion by endothelial cells. These findings suggest that angiotensin I converting enzyme inhibitor inhibits endothelin-I secretion by the accumulation of endogenous bradykinin in endothelial cells and that the inhibition of endothelin-I secretion by bradykinin is mediated via B2 receptors.