Met-Arg-Trp derived from Rubisco lowers blood pressure via prostaglandin D2-dependent vasorelaxation in spontaneously hypertensive rats

Met-Arg-Trp (MRW) has been isolated as an inhibitor for angiotensin I-converting enzyme (ACE) from a pepsin–pancreatin digest of spinach ribulose bisphosphate carboxylase/oxygenase (Rubisco) (IC50 = 0.6 μM). It has been reported that hypotensive activity of ACE-inhibitory peptides derived from food proteins are weakened in spontaneously hypertensive rats older than 25 weeks (old SHR). However, MRW reduced blood pressure after oral administration at a dose of 5 mg/kg in old SHR as well as in younger SHR. MRW exhibited vasorelaxing activity above 1 μM in isolated mesenteric artery from adult and old SHR. The vasorelaxing activity of MRW was blocked by indomethacin and BW A868C, a cyclooxygenase inhibitor and an antagonist for DP1 receptor, respectively. However, NG-nitro-l-arginine methyl ester, an inhibitor for nitric oxide synthase, had no effect on the relaxation. The hypotensive activity of MRW was also blocked by indomethacin and BW A868C, respectively, in adult and old SHR. Taken together, the vasorelaxing and hypotensive activities of MRW may be mediated by prostaglandin D2 and the DP1 receptor. These findings suggest that the hypotensive activity of MRW is mainly caused by vasorelaxation rather than by ACE-inhibition.