Bradykinin suppresses endothelin-induced contraction of coronary, renal and femoral arteries through its B2-receptor on the endothelium.
Effect of bradykinin (BK) on endothelin-1 (ET-1)-induced vasoconstriction and its mechanism were investigated. The development of isometric force of arterial rings of canine coronary, renal and femoral arteries was recorded using a organ bath containing Krebs-Henseleit buffer aerated with 95% O2 and 5% CO2. ET-1 at more than 10(-9) M dose-dependently induced vascular contraction similarly among the three arteries. BK at more than 10(-8) M dose-dependently suppressed the ET-1-induced vasoconstriction only in the presence of endothelium, and the effect of BK was largest in the coronary arteries. The BK-induced suppression was not affected by addition of des-Arg9-[Leu8]-BK, an antagonist for B1-receptor, but did be completely reversed by addition of B2-receptor antagonist (10(-6) M) [D-Arg0,Hyp3,Thi5,8,D-Phe7]-BK. The BK's suppression of the ET-1-induced vasoconstriction was partly reversed by additions of each 10(-5) of Ng-nitro-L-arginine, a substrate inhibitor of nitric oxide, methylene blue, an inhibitor of soluble guanylate cyclase, or indomethacin, an inhibitor of cyclooxygenase. The reversing effects of methylene blue and indomethacin were additive. BK suppresses the ET-1-induced vasoconstriction through B2-receptor on the endothelium. Both endothelial nitric oxide and prostaglandin(s) are participated in the BK's effect.
Ohde
H
H
Department of Drug Research, Fujimoto Pharmaceutical Co., Osaka, Japan.
Morimoto
S
S
Ohnishi
K
K
Yamaoka
E
E
Fukuo
K
K
Yasuda
O
O
Ogihara
T
T
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005263:Femoral Artery / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects*; D007700:Kinetics; D008751:Methylene Blue / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D019335:Nitroarginine; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000502:physiology*; D012077:Renal Artery / Q000187:drug effects / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*
D016232:Endothelins; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D019335:Nitroarginine; D001120:Arginine; D001920:Bradykinin; D008751:Methylene Blue; D007213:Indomethacin