A Potent Hypotensive Peptide, Novokinin, Induces Relaxation by AT₂- and IP-Receptor-Dependent Mechanism in the Mesenteric Artery from SHRs

Abstract

In this study, we found that novokinin (Arg-Pro-Leu-Lys-Pro-Trp), a potent hypotensive peptide acting through the AT₂ receptor, has vasorelaxing activity in the mesenteric artery isolated from spontaneously hypertensive rats. The vasorelaxing activity was significantly blocked by PD123319, indomethacin, and CAY10441, which are an AT₂ receptor antagonist, a cyclooxygenase inhibitor, and an IP receptor antagonist, respectively. N^G-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase, did not block the vasorelaxing activity. These results suggest that the vasorelaxing activity of novokinin, which contributes to the hypotensive effect, is mainly mediated by prostaglandin I₂ (prostacyclin) and the IP receptor downstream of the AT₂ receptor.