Effect of a leukotriene receptor antagonist on LTC4 vasoconstriction in rat stomach.
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.
Yonei
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Research Service, Veterans Administration Medical Center West Los Angeles, California.
Guth
P H
PH
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D005753:Gastric Mucosa / Q000187:drug effects / Q000502:physiology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009130:Muscle, Smooth / Q000098:blood supply; D011422:Propionates / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D013189:SRS-A / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013270:Stomach / Q000098:blood supply*; D014661:Vasoconstriction / Q000187:drug effects*; D014699:Venules / Q000187:drug effects / Q000502:physiology
D011422:Propionates; D011804:Quinolines; D013189:SRS-A; C059141:verlukast