Vasorelaxant and Antihypertensive Effects That Are Dependent on the Endothelial NO System Exhibited by Rice Bran-Derived Tripeptide

We recently identified a novel, potent antihypertensive peptide, Leu-Arg-Ala (LRA; minimum effective dose = 0.25 mg/kg), from rice bran protein. In this study, we found that LRA potently relaxed mesenteric arteries isolated from spontaneously hypertensive rats (SHRs) (EC50 = 0.1 μM). In contrast, the vasorelaxant activity of each amino acid that constitutes the LRA tripeptide was remarkably attenuated. The LRA-induced vasorelaxant activity was inhibited by N(G)-nitro-l-arginine methyl ester (L-NAME; NO synthase [NOS] inhibitor) but not by an antagonist of bradykinin B2 and Mas receptors or by a phosphoinositide 3-kinase inhibitor. The antihypertensive effect induced after the oral administration of LRA was inhibited by L-NAME. LRA also induced the phosphorylation of endothelial NOS in human umbilical vein endothelial cells. Taken together, LRA may exhibit antihypertensive effects via NO-mediated vasorelaxation. LRA is the first example of a NO-dependent vasorelaxant peptide identified from rice bran protein.