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.
Matsui
Toshiro
T
Division of Bioscience and Bioenvironmental Sciences, Faculty of Agriculture, Graduate School of Kyushu University, Tsukuba, Japan. tmatsui@agr.kyushu-u.ac.jp
Hayashi
Atsumi
A
Tamaya
Kei
K
Matsumoto
Kiyoshi
K
Kawasaki
Terukazu
T
Murakami
Kazuo
K
Kimoto
Ko-ichi
K
D000375:Aging; D000803:Angiotensin I / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D000959:Antihypertensive Agents / Q000097:blood / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004151:Dipeptides / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000235:genetics
D000959:Antihypertensive Agents; D004151:Dipeptides; C414029:valyltyrosine; D000804:Angiotensin II; D000803:Angiotensin I