Differential effect of 5- and 15-lipoxygenase products on
ischemically sensitive abdominal visceral c fiber afferents.
Pan, Hui-Lin, Gregory L. Stahl, and John C. Longhurst.
Division of Cardiovascular Medicine, Departments of Internal
Medicine and Human Physiology, University of California, Davis,
Davis, California 95616
APStracts 2:0037H, 1995.
The effect of 5- and 15-lipoxygenase products, leukotriene B4 (LTB4)
and (8R,15S)-dihydroxyeicosa(5E-9,11,13Z)tetraenoic acid (8R,15S
-diHETE), on ischemically sensitive abdominal visceral C fiber
afferents was evaluated in the present study since this system is of
importance in sensitizing cutaneous afferents. Single unit activity
of abdominal visceral C fiber afferents was recorded from the right
thoracic sympathetic chain of anesthetized cats during 5 min of
ischemia. Inhibition of 5-lipoxygenase with WY-50,295 tromethamine (5
mg/kg, iv) augmented the impulse activity from 0.48+/-0.15 to 0.79+/-0.24
imp/sec (p<0.05) in 7 ischemically sensitive afferents. Conversely,
topical application of LTB4 (125 ng) directly onto the receptive
field attenuated impulse activity of 10 ischemically sensitive C
fiber afferents from 0.82+/-0.23 to 0.42+/-0.10 imp/sec (p<0.05). In
additional cats, application of 8R,15S-diHETE (125 ng) onto the
receptive field augmented the impulse activity of 9 ischemically
sensitive C fiber afferents (0.48+/-0.15 to 0.70+/-0.15 imp/sec, p<0.05)
and significantly decreased the mechanical threshold of these 9
afferents, while application of 8S,15S-diHETE (125 ng), a
stereoisomer of 8R,15S-diHETE, attenuated the impulse activity from
0.77+/-0.48 to 0.45+/-0.13 imp/sec (p<0.05) in 6 additional ischemically
sensitive C fiber afferents. In animals pretreated with aspirin (50
mg/kg, iv, n=6) or 8S,15S-diHETE (125 ng, n=6), WY-50,295
tromethamine (5 mg/kg, iv) still potentiated the impulse activity of
ischemically sensitive C fiber afferents. These data indicate that
8R,15S-diHETE interacts with stereospecific receptors to sensitize,
while LTB4 reduces, the response of abdominal visceral afferents to
ischemia. Furthermore, the data suggest that the augmented response
of afferents to abdominal ischemia following inhibition of 5
-lipoxygenase is, at least in part, independent of shunting to
cyclooxygenase or 15-lipoxygenase system.
Received 25 August 1994; accepted in final form 31 January 1995.
APS Manuscript Number H770-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 February 1995.