Potentiation of bradykinin-induced nociceptive response by arachidonate metabolites in dogs.
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 (less than 1 nmol), but not to high doses (3-5 nmol), was markedly suppressed by infusion of indomethacin (0.54 mumol/min) into the splenic artery. During indomethacin infusion, the reflex hypertensive response to low doses of bradykinin was potentiated dose dependently by the following arachidonic acid metabolites (ED50): prostaglandin (PG)I2 (2.9 nmol) greater than or equal to PGH2 (4.4) greater than PGE2 (14) = thromboxane (TX)A2(15) greater than PGD2 (greater than 100). Leukotrienes B4, C4 and D4 showed practically no activity. This potentiating effect lasted up to 20 min after injection, particularly with PGE2. These results may not exclude the role of PGI2 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).
D000818:Animals; D001920:Bradykinin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004285:Dogs; D004357:Drug Synergism; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007269:Injections, Intra-Arterial; D007975:Leukotriene B4 / Q000494:pharmacology; D008297:Male; D010146:Pain / Q000139:chemically induced*; D010147:Pain Measurement; D011453:Prostaglandins / Q000494:pharmacology*; D013189:SRS-A / Q000494:pharmacology; D013157:Splenic Artery; D013931:Thromboxanes / Q000494:pharmacology
D005231:Fatty Acids, Unsaturated; D011453:Prostaglandins; D013189:SRS-A; D013931:Thromboxanes; D007975:Leukotriene B4; D001920:Bradykinin; D007213:Indomethacin