Possible role of leukotrienes in hypoxic contraction of canine isolated basilar artery.
1. Hypoxia reversibly increased isometric tension in unstimulated canine isolated basilar artery rings. 2. Nordihydroguaiaretic acid (NDGA; 5 x 10(-6) M), an inhibitor of lipoxygenase and quinacrine (10(-5) M), which blocks the release of arachidonic acid from phospholipids by inhibiting the enzyme phospholipase A2, blocked hypoxia-induced contractions. 3. The preferential leukotriene D4 (LTD4) antagonist, L-660,711, also inhibited the hypoxia-induced contractions in concentrations ranging from 10(-8) M to 10(-5) M. The effects seen were statistically significant (P less than 0.05). Two components of inhibition were seen. 4. Arachidonic acid (5 micrograms ml-1) caused contraction of the isolated basilar artery rings. This response was inhibited by NDGA (5 x 10(-6) M) and L-660,711 (10(-5) M). 5. The LTD4 (10(-8) M-10(-7) M)-induced contraction was relaxed by L-660,711 in a dose-dependent manner. Both the contraction caused by LTD4 as well as that caused by hypoxia were relaxed by 5 x 10(-6) M adenosine. 6. Leukotriene(s) may be involved in hypoxia-induced contraction of canine isolated basilar artery. However, they may not be the sole mediator(s).
Department of Pharmacology & Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
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D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology; D001488:Basilar Artery / Q000503:physiopathology; D004285:Dogs; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D020024:Leukotriene Antagonists; D015289:Leukotrienes / Q000502:physiology*; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D009119:Muscle Contraction / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D011422:Propionates / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D013189:SRS-A / Q000037:antagonists & inhibitors / Q000494:pharmacology
D020024:Leukotriene Antagonists; D015289:Leukotrienes; D011422:Propionates; D011804:Quinolines; D013189:SRS-A; D016718:Arachidonic Acid; C059141:verlukast; D009637:Masoprocol; D011796:Quinacrine