Ramiprilat Enhances Endothelial Autacoid Formation by Inhibiting Breakdown of Endothelium‐Derived Bradykinin
Ramiprilat Enhances Endothelial Autacoid Formation by Inhibiting Breakdown of Endothelium‐Derived Bradykinin
复制标题
雷米普利拉通过抑制内皮衍生的缓激肽的分解来增强内皮自体形成
作者：
G. Wiemer;Bemward A. Scholkens;R. Becker;R. Busse
我们研究了是否抑制血管紧张素转换酶刺激一氧化氮和前列环素的形成，在培养的人和牛内皮细胞的内皮衍生缓激肽的积累增强。一氧化氮的形成通过细胞内环GMP积累、前列环素释放通过特异性放射免疫测定来评估。雷米普利拉抑制血管紧张素转换酶的剂量和时间依赖性增加一氧化氮和前列环素的形成。这些增加在10分钟内达到峰值，并维持至少60分钟。一氧化氮合酶的立体特异性抑制剂精氨酸-硝基-精氨酸完全消除了雷米普利诱导的环GMP增加。B2-激肽受体拮抗剂Hoe 140（0.1 μM）可显著减弱环鸟苷酸（cGMP）的蓄积，并消除前列环素释放的增加。内皮细胞上清液与雷米普利拉（0.3 μM）孵育15分钟，在用作检测组织的未处理内皮细胞中引起显著的一氧化氮释放（通过guanyh/1环化酶测定评估）。用Hoe 140预孵育检测细胞完全消除了这种一氧化氮释放。这些数据表明，培养的内皮细胞从不同的物种是能够产生和释放缓激肽到细胞外空间的量，导致持续刺激一氧化氮和前列环素的形成，只要缓激肽降解是防止血管紧张素转化酶抑制。因此，血管紧张素转换酶抑制剂对高血压患者内皮血管功能的保护作用可以通过内皮源性缓激肽的局部蓄积来解释，缓激肽以自分泌和旁分泌的方式作为内皮自分泌物形成的有效刺激。
We studied whether inhibition of angiotensin converting enzyme stimulates the formation of nitric oxide and prostacyclin in cultured human and bovine endothelial cells by an enhanced accumulation of endothelium-derived bradykinin. Nitric oxide formation was assessed in terms of intracellular cyclic GMP accumulation, prostacyclin release by a specific radioimmunoassay. Inhibition of angiotensin converting enzyme by ramiprilat dose- and time-dependently increased the formation of nitric oxide and prostacyclin. These increases, peaking within 10 minutes, were maintained for at least 60 minutes. The ramiprilat-induced cyclic GMP increase was completely abolished by the stereospecific inhibitor of nitric oxide synthase, ArG-nitro-Larginine. The B2-kinin receptor antagonist, Hoe 140 (0.1 μM), markedly attenuated the cyclic GMP accumulation and abolished the increase in prostacyclin release. The supernatant of endothelial cells, incubated with ramiprilat (0.3 μM) for 15 minutes, elicited a significant nitric oxide release (as assessed by a guanyh/1 cyclase assay) in untreated endothelial cells used as detector tissue. Preincubation of the detector cells with Hoe 140 completely abolished this nitric oxide release. These data indicate that cultured endothelial cells from different species are capable of producing and releasing bradykinin into the extracellular space in amounts that lead to a sustained stimulation of nitric oxide and prostacyclin formation, provided that bradykinin degradation is prevented by angiotensin converting enzyme inhibition. Thus, the protective effect of angiotensin converting enzyme inhibitors observed on endothelial vasomotor function in hypertension may be explained by the local accumulation of endothelium-derived bradykinin that acts in an autocrine and paracrine manner as potent stimulus for endothelial autacoid formation.
肾素和非肾素介导的转化酶抑制剂的抗高血压作用。
影响因子：
19.6
作者：
Zusman,RM
通讯作者：
Zusman,RM
内皮肾素-血管紧张素途径：血管紧张素细胞内合成和分泌的证据。
影响因子：
20.1
作者：
Kifor,I;Dzau,VJ
通讯作者：
Dzau,VJ
缓激肽通过激活培养的猪主动脉内皮细胞中的 B2 激肽受体来刺激环 GMP 的产生。
DOI：
--
发表时间：
1990
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Schini,VB;Boulanger,C;Regoli,D;Vanhoutte,PM
通讯作者：
Vanhoutte,PM