AJP - Gastrointestinal and Liver Physiology, Vol 259, Issue 1 147-G154, Copyright © 1990 by American Physiological Society
Effect of a leukotriene receptor antagonist on LTC4 vasoconstriction in rat stomach
Y. Yonei and P. H. Guth
Research Service, Veterans Administration Medical Center West Los Angeles, California.
With the use of an in vivo microscopy technique in
anesthetized-laparotomized rats, the effect of L660,711, a
cysteinyl-leukotriene (LT) receptor antagonist, on the gastric submucosal
microvascular response to leukotrienes was studied. The direct application
of 50-400 nM LTC4 onto the exposed submucosal vasculature caused
constriction of both arterioles (maximum constriction: 24 +/- 3%) and
venules (26 +/- 3%), whereas LTD4 had no significant effect. Pretreatment
with 5 mg/kg L660,711 intragastrically significantly attenuated the
LTC4-induced vasoconstriction. The submucosal application of 2 x 10(-7) to
2 x 10(-2) M L660,711 dose dependently inhibited the 400 nM LTC4-induced
vasoconstriction. The IC50 of L660,711, preapplied to the gastric submucosa
for 15 min, was 4.4 x 10(-4) M in arterioles and 3.9 x 10(-4) M in venules,
and 3.6 x 10(-5) M and 3.2 x 10(-5) M, respectively, when it was applied
simultaneously with LTC4. Schild plot analysis revealed that L660,711 was
not a pure competitive receptor antagonist. L660,711 had no significant
effects on epinephrine- or vasopressin-induced arteriolar constriction. In
conclusion, L660,711 significantly antagonizes the gastric microvascular
effects of LTC4, but not those of other vasoconstrictors, and appears to be
a useful new tool for studying LTC4 effects.
