Inhibition of endopeptidase-24.15 decreases blood pressure in normotensive rats.
Inhibition of endopeptidase-24.15 decreases blood pressure in normotensive rats.
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抑制内肽酶 24.15 可降低血压正常大鼠的血压。
DOI：
10.1161/01.hyp.18.3.360
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Molineaux,CJ
中科院分区：
文献类型：
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作者：
Genden,EM;Molineaux,CJ
有效的血管舒张肽缓激肽在体外被金属酶内肽酶-24.15（E.C.3.4.24.15）在Phe 5-Ser 6键处裂解。我们现在报告，静脉输注N-[1-（R，S）-羧基-3-苯丙基]-Ala-Ala-Phe-对-氨基苯甲酸酯，一种内肽酶-24.15的特异性活性位点定向抑制剂，在戊巴比妥麻醉的血压正常大鼠中产生高达50 mm Hg的平均动脉压立即下降。动脉压在5分钟内恢复。B2缓激肽拮抗剂[Arg 0，Hyp 3，Thi 5，8，D-Phe 7]-缓激肽可减弱抑制剂治疗引起的平均动脉压降低。内肽酶-24.15抑制剂增强了静脉内缓激肽输注的扩张作用，使肽的最大作用增加了47%，并使效力增加了近10倍，而对动脉内缓激肽的反应受抑制剂的影响较小。这些结果支持内肽酶-24.15在内源性和外源性缓激肽失活中的作用，并表明该酶直接参与血压的控制。
The potent vasodilatory peptide bradykinin is cleaved at the Phe5-Ser6 bond in vitro by the metalloenzyme endopeptidase-24.15 (E.C.3.4.24.15). We now report that intravenous infusion of N-[1-(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate, a specific active site-directed inhibitor of endopeptidase-24.15, produces an immediate drop in mean arterial pressure of as much as 50 mm Hg in pentobarbital-anesthetized, normotensive rats. Arterial pressure recovers within 5 minutes. The B2 bradykinin antagonist [Arg0,Hyp3,Thi5,8,D-Phe7]-bradykinin attenuates the decrease in mean arterial pressure resulting from treatment with the inhibitor. The endopeptidase-24.15 inhibitor potentiates the hypotensive effect of intravenous bradykinin infusion, increasing the maximal effect of the peptide by 47% and increasing the potency by almost 10-fold, while the response to intra-arterial bradykinin is less affected by the inhibitor. These results support a role for endopeptidase-24.15 in the inactivation of endogenous and exogenous bradykinin and suggest a direct involvement of the enzyme in the control of blood pressure.