Designing Potent Derivatives of Ovokinin(2-7), an Anti-hypertensive Peptide Derived from Ovalbumin
Designing Potent Derivatives of Ovokinin(2-7), an Anti-hypertensive Peptide Derived from Ovalbumin
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DOI：
10.1271/bbb.65.736
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发表时间：
2001-01
期刊：
影响因子：
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通讯作者：
N. Matoba;Yuko Yamada;H. Usui;Ryusuke Nakagiri;M. Yoshikawa
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文献类型：
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作者：
N. Matoba;Yuko Yamada;H. Usui;Ryusuke Nakagiri;M. Yoshikawa
我们通过取代Ovokinin(2-7)(RADHPF)的氨基酸残基，得到了一种有效的降压肽RPFHPF。在麻醉Wistar大鼠静脉注射后，设计的多肽[Pro2，Phe3]-Ovokinin(2-7)在10 mg/kg剂量下具有持久的降压作用，而Ovokinin(2-7)在100 mg/kg剂量下也只有短暂的降压作用。清醒自发性高血压大鼠(SHR)灌胃给药后，[Pro2，Phe3]-Ovokinin(2-7)呈剂量依赖性地显著降低血压。值得注意的是，[Pro2，Phe3]-Ovokinin(2-7)的最小有效剂量为0.3 mg/kg，约为Ovokinin(2-7)的1/30。另一方面，口服[Pro2，Phe3]-Ovokinin(2-7)即使在3 mg/kg的剂量下，对正常血压的Wistar-京都大鼠(WKYS)也没有明显的降压作用。综上所述，[Pro2，Phe3]-Ovokinin(2-7)是一种理想的、有效的降压肽，口服时对正常血压影响不大。
We obtained a potent anti-hypertensive peptide, RPFHPF, by replacing the amino acid residues of ovokinin(2-7) (RADHPF), an orally active anti-hypertensive peptide derived from ovalbumin. After intravenous administration in anesthetized Wistar rats, the designed peptide [Pro2, Phe3]-ovokinin(2-7) had a long-lasting hypotensive activity at a dose of 10 mg/kg, while that of ovokinin(2-7) was only transient even at a dose of 100 mg/kg. After oral administration in conscious spontaneously hypertensive rats (SHRs), [Pro2, Phe3]-ovokinin(2-7) significantly lowered the systolic blood pressure in a dose-dependent manner. It is noteworthy that the minimum effective dose of [Pro2, Phe3]-ovokinin(2-7) was 0.3 mg/kg, about one-thirtieth of that of ovokinin(2-7). On the other hand, orally administered [Pro2, Phe3]-ovokinin(2-7) did not show any significant hypotensive effect in normotensive Wistar-Kyoto rats (WKYs) even at a dose of 3 mg/kg. Taken together, [Pro2, Phe3]-ovokinin(2-7) proved to be an ideal, potent anti-hypertensive peptide with little effect on normal blood pressure when given orally.