Antihypertensive peptides are present in aorta after oral administration of sour milk containing these peptides to spontaneously hypertensive rats.
Absorption of inhibitory peptides to angiotensin I-converting enzyme, L-valyl-L-prolyl-L-proline and L-isoleucyl-L-prolyl-L-proline, was studied in spontaneously hypertensive rats and normotensive Wistar-Kyoto rats after an oral administration of Calpis sour milk, which contains these peptides. Six hours after the administration of Calpis sour milk or saline to spontaneously hypertensive rats or normotensive Wistar-Kyoto rats, the blood pressure was measured and rats were killed. Abdominal aorta, lung, kidney, heart and brain were excised, homogenized and solubilized by detergent treatments. Angiotensin I-converting enzyme activity in the solubilized fractions from the abdominal aorta was significantly lower in spontaneously hypertensive rats given the sour milk than in the rats given saline. L-Valyl-L-prolyl-L-proline and L-isoleucyl-L-prolyl-L-proline were detected by HPLC in the heat-treated solubilized fraction from the abdominal aorta of spontaneously hypertensive rats given the sour milk. In contrast, the tripeptides were not detected in rats given saline, or in normotensive Wistar-Kyoto rats given the sour milk or saline. These data suggest that L-valyl-L-prolyl-L-proline and L-isoleucyl-L-prolyl-L-proline in the Calpis sour milk are absorbed directly without being decomposed by digestive enzymes, reach the abdominal aorta, inhibit the angiotensin I-converting enzyme, and show antihypertensive effects in spontaneously hypertensive rats.
Masuda
O
O
R&D Center, The Calpis Food Industry Co., Ltd., Fuchinobe, Sagamihara, Japan.
Nakamura
Y
Y
Takano
T
T
D000284:Administration, Oral; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics*; D001011:Aorta / Q000187:drug effects* / Q000201:enzymology; D002851:Chromatography, High Pressure Liquid; D005285:Fermentation; D007408:Intestinal Absorption; D008297:Male; D008892:Milk; D010455:Peptides / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity; D014018:Tissue Distribution
D000596:Amino Acids; D000959:Antihypertensive Agents; D010455:Peptides; D007703:Peptidyl-Dipeptidase A