EFFECTS OF INHIBITORS OF ARACHIDONIC-ACID METABOLISM AND CALCIUM ENTRY ON RESPONSES TO ACETYLCHOLINE, POTASSIUM AND NOREPINEPHRINE IN THE ISOLATED CANINE SAPHENOUS-VEIN

  • 1 January 1983
    • journal article
    • research article
    • Vol. 225  (3) , 720-728
Abstract
Whether interference with the metabolism of arachidonic acid or the entry of extracellular Ca affects the responses of the canine saphenous vein to acetylcholine, K or norepinephrine was studied. Rings of canine saphenous vein, with or without endothelium, were suspended in organ chambers filled with physiological salt solution and set at their optimal length for isometric tension recording. Removal of the endothelium, confirmed by the absence of the characteristic relaxation induced by thrombin in intact rings, did not affect concentration-response curves to acetylcholine or norepinephrine. The cyclooxygenase inhibitor, indomethacin, augmented the response to acetylcholine. This effect was comparable in rings with and without endothelium and in rings pretreated with phentolamine. Indomethacin did not alter the response to norepinephrine but augmented that to K. Similar results were obtained with the cyclooxygenase inhibitors, acetylsalicylic acid and meclofenamate. The antioxidant and lipoxygenase inhibitor nordihydroguaiaretic acid and the cyclooxygenase/lipoxygenase inhibitor phenidone blocked the ability of indomethacin to augment acetylcholine- and K-induced contractions. Arachidonic acid-induced contractions were not blocked by indomethacin but were inhibited by nordihydroguaiaretic acid, phenidone and the Ca entry blockers diltiazem and nimodipine. Diltiazem and nimodipine inhibited responses to K and acetylcholine without affecting those to norepinephrine. The augmentation by indomethacin of K- and acetylcholine-evoked contractions was inhibited by diltiazem and nimodipine. In rings of femoral artery denuded of endothelium, indomethacin had no effect on the responses to acetylcholine, norepinephrine or K. In the canine saphenous vein but not in the femoral artery, activation of the lipoxygenase pathway for the metabolism of arachidonic acid apparently preferentially augments contractions which depend upon the entry of extracellular Ca.