The endothelium-dependent vasodilator effect of acetylcholine: characterization of the endothelial relaxing factor with inhibitors of arachidonic acid metabolism.
Acetylcholine (ACh) caused concentration-dependent relaxation of strips of rabbit thoracic aorta precontracted with noradrenaline if the endothelium was intact. More than ten-fold higher concentrations of ACh also stimulated the release of prostacyclin (PGI2) and PGE2 from the strips. De-endothelialized strips released much smaller amounts of prostaglandins and contracted slightly to ACh. The endothelium-dependent vasodilation was resistant to cyclooxygenase inhibition by indomethacin, flurbiprofen and diclofenac. However, it could be reversed by six different inhibitors of lipoxygenase (nordihydroguaiaretic acid, phenidone, eicosatetraynoic acid, nafazatrom, compound BW 755C and caffeic acid). BW 755C and caffeic acid, a selective inhibitor of 5-lipoxygenase, had comparatively weak effects on the relaxation. Eicosatetraynoic acid, which probably does not inhibit C-5-lipoxygenase, completely reversed the effect of ACh. It is concluded that ACh relaxes strips of rabbit aorta by a mechanism in involving a non-cyclooxygenase metabolite of arachidonic acid of endothelial origin. This compound is probably not a product of C-5-lipoxygenase.
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001685:Biological Factors; D002241:Carbohydrates / Q000502:physiology; D016861:Cyclooxygenase Inhibitors; D004727:Endothelium / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D016859:Lipoxygenase Inhibitors; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology*
D001095:Arachidonic Acids; D001685:Biological Factors; D002241:Carbohydrates; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D014665:Vasodilator Agents; D016718:Arachidonic Acid; C033031:smooth muscle inhibitory factor; D000109:Acetylcholine; D009638:Norepinephrine