Designing potent derivatives of ovokinin(2-7), an anti-hypertensive peptide derived from ovalbumin.
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.
Matoba
N
N
Research Institute for Food Science, Kyoto University, Uji, Japan.
Yamada
Y
Y
Usui
H
H
Nakagiri
R
R
Yoshikawa
M
M
D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D008297:Male; D010047:Ovalbumin / Q000138:chemical synthesis* / Q000494:pharmacology; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000494:pharmacology; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar
D000959:Antihypertensive Agents; D010446:Peptide Fragments; D010455:Peptides; C119914:ovalbumin (359-364); D010047:Ovalbumin