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

Abstract

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.