NEURAL AND ENDOCRINE CIRCUITS MEDIATING INHIBITION OF BRADYKININ-INDUCED PLASMA EXTRAVASATION BY SUBCUTANEOUS AND SPINAL-INTRATHECAL NICOTINE

In this study we evaluated the mechanisms underlying s.c, and spinal i ntrathecal (i.t.) nicotine inhibition of bradykinin-induced plasma ext ravasation in the knee joint of the rat (J. Pharmacol. Exp. Ther. 262: 889-895, 1992;ibid., 264: 839-844, 1993). The dose-response curve for the inhibitory action of s.c. nicotine on bradykinin-induced plasma e xtravasation was attenuated by adrenal medullectomy and by intra-artic ular perfusion of ICI-118,551 (a beta-2 adrenoceptor antagonist). In a ddition, the dose-response curve of s.c. nicotine was attenuated by ac ute surgical lumbar sympathectomy and by intra-articular phentolamine (an alpha adrenoceptor antagonist). The dose-response curve for i.t. n icotine (up to 1 mg/kg) was not attenuated by intra-articular ICI-118, 551 and was potentiated by adrenal medullectomy. The action of i.t. ni cotine was also not affected by intra-articular phentolamine or by acu te surgical lumbar sympathectomy. These results suggest that the inhib ition of bradykinin-induced plasma extravasation in the knee joint of the rat by s.c. but not i.t., nicotine is mediated through the sympath oadrenal and sympathetic system.