Abstract
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 (SBP~0h~198.0 ± 3.6 mmHg; SBP~9h~ 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. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd.