Involvement of cyclo-oxygenase-generated vasodilating eicosanoid(s) in addition to nitric oxide in endothelin-1-induced endothelium-dependent vasorelaxation in guinea pig aorta.
This study investigates the vasodilatory effects of endothelin-1 (ET-1) in isolated guinea pig aortic rings in vitro. Cumulative dose-response curves to ET-1 were constructed and ET-1 actions on prostaglandin F2 alpha (PGF2 alpha)-precontraction were studied in both endothelium-intact and endothelium-denuded preparations, in the presence or absence of a cyclooxygenase inhibitor (indomethacin) and/or nitric oxide inhibitors (NG-nitro-L-arginine methyl ester and hemoglobin). In endothelium-intact preparations, pretreatment with indomethacin (10(-5) M, 30 min), alone or in combination with NG-nitro-L-arginine methyl ester (L-NAME, 10(-4) M), significantly augmented the constrictive responses to ET-1, whereas indomethacin, L-NAME, and hemoglobin (10(-5) M) had no significant effects in the endothelium-denuded preparations. Furthermore, in PGF2 alpha-precontracted, endothelium-intact preparations, ET-1, at a dose of 10(-9) M, induced initial relaxation followed by subsequent contraction, while it only contracted the endothelium-denuded preparations. The initial relaxation was abolished by indomethacin, but not by L-NAME or hemoglobin. In addition, this relaxation was not inhibited by a specific ETA receptor antagonist, BQ-123 (6 x 10(-6) M). In addition to the involvement of nitric oxide, these results show the involvement of cyclo-oxygenase-generated vasodilating eicosanoid(s) derived from endothelium in ET-1-induced vasorelaxation in guinea pig aorta in vitro. The results also indicate that this vasorelaxation is mediated by ETB receptor activation.
Matsuda
H
H
Department of Cardiovascular Dynamics, National Cardiovascular Center Research Institute, Osaka, Japan.
Beppu
S
S
Ohmori
F
F
Yamada
M
M
Miyatake
K
K
D000818:Animals; D001011:Aorta; D015777:Eicosanoids / Q000502:physiology*; D016232:Endothelins / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D011464:Epoprostenol / Q000502:physiology; D005260:Female; D006168:Guinea Pigs; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D009924:Organ Culture Techniques; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D017466:Receptors, Endothelin / Q000502:physiology; D014664:Vasodilation / Q000502:physiology*
D015777:Eicosanoids; D016232:Endothelins; D017466:Receptors, Endothelin; D009569:Nitric Oxide; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases