A milk-derived pentapeptide reduces blood pressure in advanced hypertension in a CCK system-dependent manner
A milk-derived pentapeptide reduces blood pressure in advanced hypertension in a CCK system-dependent manner
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牛奶源五肽以 CCK 系统依赖性方式降低晚期高血压患者的血压
DOI：
10.1039/d0fo01122c
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发表时间：
2020
期刊：
影响因子：
6.1
通讯作者：
Ohinata K
中科院分区：
文献类型：
--
作者：
Koyama D ;Sasai M ;Matsumura S ;Inoue K ;Ohinata K
我们最近发现，一种激活胆囊收缩素（CCK）系统的肽能有效降低自发性高血压大鼠（SHR）在高血压发生后的血压，此后，降压药物有时效果较差。在这项研究中，我们研究了一种来自牛奶蛋白的肽在患有晚期高血压的SHR中的血管舒张和抗高血压作用。用离体SHR肠系膜动脉测定血管舒张活性，用尾套法测定体循环血压。枯草杆菌蛋白酶消化后，从牛血清白蛋白（BSA）和模型肽中释放KFWGK。KFWGK松弛肠系膜动脉，这种血管舒张活性被CCK 1受体拮抗剂lorglumide抑制。KFWGK对晚期SHR的舒张作用强于早期SHR。口服KFWGK在高血压发展后的SHR中表现出有效和持久的抗高血压作用（最小有效剂量为5 μg kg−1）。KFWGK诱导的降压作用也被CCK拮抗剂阻断，表明其激活CCK系统。总之，KFWGK，一种CCK依赖性血管舒张肽，在高血压发展后的SHR中表现出有效的降压作用。
We recently found that a peptide that activates the cholecystokinin (CCK) system effectively reduces blood pressure in spontaneously hypertensive rats (SHR) after the development of hypertension, after which hypotensive drugs are sometimes less effective. In this study, we investigated the vasorelaxation and antihypertensive effects of a peptide derived from a milk protein in SHR with advanced hypertension. The vasorelaxing activity was measured using the mesenteric artery isolated from SHR and the systemic blood pressure was measured by the tail-cuff method. KFWGK was released from bovine serum albumin (BSA) and the model peptide after subtilisin digestion. KFWGK relaxed the mesenteric artery and this vasorelaxation activity was inhibited by lorglumide, an antagonist of the CCK1 receptor. KFWGK more potently relaxed the artery from advanced-stage SHR than that from early-stage SHR. Orally administered KFWGK exhibited potent and long-lasting antihypertensive effects in SHR after the development of hypertension (the minimum effective dose was 5 μg kg−1). The KFWGK-induced antihypertensive effects were also blocked by a CCK antagonist, suggesting that it activates the CCK system. In conclusion, KFWGK, a CCK-dependent vasorelaxant peptide, exhibited potent antihypertensive effects in SHR after the development of hypertension.