Met-Arg-Trp derived from Rubisco lowers blood pressure via prostaglandin D(2)-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) (IC(50)=0.6 microM). 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 microM 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 DP(1) receptor, respectively. However, N(G)-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 D(2) and the DP(1) receptor. These findings suggest that the hypotensive activity of MRW is mainly caused by vasorelaxation rather than by ACE-inhibition.
Zhao
Hui
H
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Uji, Kyoto, Japan.
Usui
Hachiro
H
Ohinata
Kousaku
K
Yoshikawa
Masaaki
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D004334:Drug Administration Schedule; D006827:Hydantoins / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D015230:Prostaglandin D2 / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D012273:Ribulose-Bisphosphate Carboxylase / Q000737:chemistry*; D050680:Transcription Factor DP1 / Q000037:antagonists & inhibitors; D014664:Vasodilation / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D006827:Hydantoins; D010455:Peptides; D050680:Transcription Factor DP1; C058848:BW A868C; D012273:Ribulose-Bisphosphate Carboxylase; D015230:Prostaglandin D2; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin