Analysis of bradykinin-induced relaxations in the rat isolated anococcygeus muscle.
The present study investigates the mechanism(s) of action of relaxations induced by bradykinin and by electrical field stimulation (EFS) in isolated rat anococcygeus muscle, where contractile tone has been elevated with clonidine. Bradykinin, EFS, and the bradykinin B1 receptor agonist, des-Arg9-bradykinin, produced quantitatively and qualitatively similar relaxations. Bradykinin B1 receptor antagonist, [des-Arg9,Leu8]-bradykinin (1 microM), attenuated the relaxation responses of bradykinin B1 receptor agonist and inhibited bradykinin and EFS-induced relaxation responses. Bradykinin B2 receptor antagonist, [beta-(2-thienyl)-Ala5,8,D-Phe7]-bradykinin (1 microM), significantly inhibited the relaxation responses of bradykinin, EFS, and bradykinin B1 receptor agonist. Methylene blue (30 microM) and N-methylhydroxylamine (1 mM) significantly inhibited the bradykinin- and EFS-induced relaxation responses. The relaxation responses of bradykinin and EFS were not affected by captopril (5 microM), superoxide dismutase (100 U/ml), and catalase (100 U/ml). Nitric oxide synthase inhibitor, L-NG-nitro-arginine (L-NOARG, 30 microM), significantly inhibited the EFS- and bradykinin-induced relaxation responses. L-arginine (100 microM) reversed the inhibitory effect of L-NOARG on the relaxation responses of EFS and bradykinin. In addition, L-arginine potentiated the relaxation responses of EFS and bradykinin. The data of the present study suggests that bradykinin, similar to EFS, generates an endogenous nitrate, probably nitric oxide, which subsequently activates guanylate cyclase and relaxes the rat anococcygeus muscle.
Mudumbi
R V
RV
Division of Pharmacology, Glaxo Inc. Research Institute, Research Triangle Park, North Carolina 27709.
Leighton
H J
HJ
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001920:Bradykinin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D019335:Nitroarginine; D051381:Rats; D018002:Receptors, Bradykinin / Q000502:physiology; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism
D018002:Receptors, Bradykinin; D013481:Superoxides; D019335:Nitroarginine; D001120:Arginine; D002216:Captopril; D013482:Superoxide Dismutase; D001920:Bradykinin