Bradykinin contracts the pupillary sphincter and evokes ocular inflammation through release of neuronal substance P.

Bradykinin contracts the isolated rabbit sphincter pupillae muscle. The contraction produced by 10(-8) M bradykinin was resistant to atropine but not to tetrodotoxin, suggesting a non-cholinergic nervous mechanism. The contraction was blocked by specific substance P (SP) antagonists, suggesting the involvement of SP. The SP antagonists tested were [D-Pro2,D-Trp7,9]SP-(1-11) and [Arg5,D-Trp7,9]SP-(5-11). The bradykinin-induced contraction exhibited marked tachyphylaxis in contrast to that induced by SP. It appears that the tachyphylaxis reflects the depletion of a bradykinin-sensitive neuronal pool of SP. Injection of bradykinin into the vitreous chamber of the rabbit eye caused miosis and disruption of the blood-aqueous barrier (manifested as aqueous flare). A second administration of bradykinin a few hours after the first injection evoked a reduced response; the response to SP upon repeated administration was unchanged. Atropine was without effect on the response to bradykinin whereas tetrodotoxin and the SP antagonists reduced the response. The results suggest that bradykinin causes miosis and aqueous flare at least partly through local release of neuronal SP.