Tissue distribution of antihypertensive dipeptide, Val-Tyr, after its single oral administration to spontaneously hypertensive rats.
The distribution of an antihypertensive dipeptide, Val-Tyr (VY), in the tissues of spontaneously hypertensive rats (SHR) was investigated in this study. A single oral administration of VY (10 mg/kg) to 18-week-old SHR resulted in a prolonged reduction of systolic blood pressure (SBP) up to 9 h (SBP0h 198.0+/-3.6 mmHg; SBP9h 154.6+/-3.5 mmHg). As a result of VY determination, a roughly 10-fold higher increment of plasma VY level was observed at 1 h than that at 0 h, whereas thereafter the level declined rapidly. In tissues, VY was widely accumulated in the kidney, lung, heart, mesenteric artery and abdominal aorta with the area under the curve over 9 h of more than 40 pmol h/g tissue; of these a higher VY level was observed in the kidney and lung. In addition, a mean resident time (MRT) for each tissue (>5 h except for liver) revealed that VY preferably accumulated in the tissues rather than in the plasma (MRT 3.8 h). Significant reductions of tissue angiotensin I-converting enzyme activity and angiotensin II level were found in the abdominal aorta as well as in the kidney, suggesting that these organs could be a target site associated with the antihypertensive action of VY.
Matsui
Toshiro
T
Faculty of Agriculture, Graduate School of Kyushu University, Fukuoka, Japan. tmatsui@agr.kyushu-u.ac.jp
Imamura
Miho
M
Oka
Hiromi
H
Osajima
Katsuhiro
K
Kimoto
Ko-Ichi
K
Kawasaki
Terukazu
T
Matsumoto
Kiyoshi
K
D000284:Administration, Oral; D000803:Angiotensin I / Q000032:analysis / Q000378:metabolism; D000804:Angiotensin II / Q000032:analysis / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001794:Blood Pressure / Q000187:drug effects; D004151:Dipeptides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006973:Hypertension / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D014018:Tissue Distribution
D000959:Antihypertensive Agents; D004151:Dipeptides; C414029:valyltyrosine; D000804:Angiotensin II; D000803:Angiotensin I