Effect of bradykinin antagonists on bradykinin-induced plasma extravasation, venoconstriction, prostaglandin E2 release, nociceptor stimulation and contraction of the iris sphincter muscle in the rabbit.
1 The inhibition of the bradykinin-induced plasma extravasation by six bradykinin (Bk) antagonists was tested on rabbit skin. All of them showed inhibitory effects without an agonistic action in the does used. B4310 (Lys-Lys-3-Hyp-5,8-Thi-7-DPhe-Bk) was the most active antagonist and was therefore used in the subsequent experiments. 2 B4310 (5-500 nM) antagonized the bradykinin-induced reduction of the venous outflow from the rabbit isolated ear in dose-dependent manner without affecting the arterial vasoconstriction induced by angiotensin II. 3 The bradykinin-induced release of prostaglandin E2 (PGE2) from the perfused rabbit ear was reduced by 63% when B4310 (800 nM) was infused before, during and after the bradykinin injection. 4 Bradykinin was injected into the ear artery of anaesthetized rabbits and the reflex hypotensive response was used as indicator of the nociception. The response was antagonized by a local infusion of B4310 (50 and 500 nM). The antagonism was dose-dependent and reversible. The parallel shift of the dose-response curve to bradykinin suggests a competitive inhibition. However, B4310 did not antagonize acetylcholine-induced nociceptor stimulation. 5 B4310 inhibited bradykinin-induced stimulation of the trigeminal nerve which results in a substance P-mediated contraction of the iris sphincter muscle. A pA2 of 7.59 was calculated. B4310 did not inhibit capsaicin-induced contractions. 6 It is concluded that B4310 inhibits specifically five different actions of bradykinin which are related to its possible pathophysiological role.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015232:Dinoprostone; D005260:Female; D066298:In Vitro Techniques; D007498:Iris / Q000187:drug effects; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D011458:Prostaglandins E / Q000378:metabolism; D051381:Rats; D011983:Receptors, Purinergic / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply; D012879:Skin Physiological Phenomena; D014661:Vasoconstriction / Q000187:drug effects
D011458:Prostaglandins E; D011983:Receptors, Purinergic; D015232:Dinoprostone; D000109:Acetylcholine; D001920:Bradykinin