A potent hypotensive peptide, novokinin, induces relaxation by AT2- and IP-receptor-dependent mechanism in the mesenteric artery from SHRs.
In this study, we found that novokinin (Arg-Pro-Leu-Lys-Pro-Trp), a potent hypotensive peptide acting through the AT(2) 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 AT(2) 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 I(2) (prostacyclin) and the IP receptor downstream of the AT(2) receptor.
Yamada
Yuko
Y
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan.
Yamauchi
Daiki
D
Yokoo
Megumi
M
Ohinata
Kousaku
K
Usui
Hachiro
H
Yoshikawa
Masaaki
M
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D014664:Vasodilation / Q000187:drug effects*
D000959:Antihypertensive Agents; C511871:Arg-Pro-Leu-Lys-Pro-Trp; D009842:Oligopeptides; D019331:NG-Nitroarginine Methyl Ester