DIFFERENTIAL EFFECT OF 5-LIPOXYGENASE AND 15-LIPOXYGENASE PRODUCTS ONISCHEMICALLY SENSITIVE ABDOMINAL VISCERAL AFFERNENTS

The effects of 5- and 15-Lipoxygenase products, leukotriene B-4 (LTB(4 )) and (8R, 15S)-dihydroxyeicosa(5E-9,11,13Z)tetraenoic acid (8R,15S-d iHETE), on ischemically sensitive abdominal visceral C fiber afferents were evaluated, because this system is important in sensitizing cutan eous afferents. Single-unit activity of abdominal visceral C fiber aff erents was recorded from the right thoracic sympathetic chain of anest hetized cats during 5 min of ischemia Inhibition of 5-lipoxygenase wit h WY-50295 tromethamine (5 mg/kg iv) augmented the impulse activity fr om 0.48 +/- 0.15 to 0.79 +/- 0.24 impulses/s (P < 0.05) in seven ische mically sensitive afferents. Conversely, topical application of LTB(4) (125 ng) directly onto the receptive field attenuated impulse activit y of 10 ischemically sensitive C fiber afferents from 0.82 +/- 0.23 to 0.42 +/- 0.10 impulses/s (P < 0.05). In additional cats, application of 8R,15S-diHETE (125 ng) onto the receptive held augmented the impuls e activity of nine ischemically sensitive C fiber afferents (from 0.48 +/- 0.15 to 0.70 +/- 0.15 impulses/s, P < 0.05) and significantly dec reased the mechanical threshold of these nine afferents, whereas appli cation of 8S,15S-diHETE (125 ng), a stereoisomer of 8R,15S-diHETE, att enuated the impulse activity from 0.77 +/- 0.48 to 0.45 +/- 0.13 impul ses/s (P < 0.05) in six additional ischemically sensitive C fiber affe rents. In animals pretreated with aspirin (50 mg/kg iv, n = 6) or 8S,1 5S-diHETE (125 ng, n = 6), WY-50295 tromethamine (5 mg/kg iv) still po tentiated the impulse activity of ischemically sensitive C fiber affer ents. These data indicate that 8R,15S-diHETE interacts with stereospec ific receptors to sensitize, whereas LTB(4) reduces, the response of a bdominal visceral afferents to ischemia. Furthermore the data suggest that the augmented response of afferents to abdominal ischemia after i nhibition of 5-lipoxygenase is, at least in part, independent of shunt ing to the cyclooxygenase or 15-lipoxygenase system.