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.

Depressor effect induced by dipeptide, Val-Tyr, in hypertensive transgenic mice is due, in part, to the suppression of human circulating renin-angiotensin system.

1. In the present study, the depressor action of the dipeptide Val-Tyr, with an in vivo antihypertensive effect, was investigated in transgenic mice carrying the human renin gene cross-mated with mice bearing the human angiotensinogen gene (Tsukuba Hypertensive Mouse; THM). 2. Single oral administration of Val-Tyr (0.1 mg/g) to 11-week-old THM resulted in a prolonged reduction of blood pressure for up to 9 h. The effect clearly demonstrated that the Val-Tyr absorbed acted on the enhanced human renin-angiotensin system (RAS). 3. After Val-Tyr administration, an approximate eightfold higher increment of plasma Val-Tyr was observed at 1 h (3406 +/- 211 fmol/mL plasma) compared with the level observed at 0 h; plasma concentrations of Val-Tyr returned to baseline levels at 6 h. 4. Transient changes in plasma concentrations of angiotensin (Ang) I and AngII only at 1 h were consistent with plasma Val-Tyr concentrations, suggesting that that the long-lasting reduction in blood pressure was achieved by the latent hypotensive mechanism of Val-Tyr and not by transient suppression of the circulatory RAS. 5. Ageing of the THM greatly affected the depressor action of Val-Tyr, with no significant reduction in blood pressure observed in 18- and 24-week-old THM.