Potentiation of bradykinin-induced nociceptive response by arachidonate metabolites in dogs

Abstract Bradykinin was injected retrogradely into a branch of the splenic artery of lightly anesthetized dogs, and the reflex hypertensive response was used as an indicator of the nociception. The reflex hypertensive response to low doses of bradykinin ( 50 ): prostaglandin (PG)I 2 (2.9 nmol) ≥ PGH 2 (4.4) > PGE 2 (14) = thromboxane (TX)A 2 (15) > PGD 2 (> 100). Leukotrienes B 4 , C 4 and D 4 showed practically no activity. This potentiating effect lasted up to 20 min after injection, particularly with PGE 2 . These results may not exclude the role of PGI 2 as a major candidate for involvement in bradykinin-induced nociception, although a selective TX synthetase inhibitor (OKY-046) showed a weak analgesic effect (only 1 30 that of indomethacin).