The effect of morphine in rat small mesenteric arteries

We investigated the effect of morphine in phenylephrine (PE)- or KCl-precontracted rat small mesenteric arteries. Morphine (10− 6-10− 4 M) administration caused concentration-dependent relaxation responses in small mesenteric arteries precontracted by PE or KCl. Removal of endothelium did not significantly alter the relaxation responses to morphine. The relaxant responses to morphine were partially inhibited by pre-treatment of tissues with naloxone (NAL, 10− 5 M) for 20 min. The inhibitory effect of NAL on relaxant responses to morphine in PE- or KCl-precontracted arteries did not differ significantly between endothelium-intact and endothelium-denuded preparations. Incubation of endothelium-intact or endothelium-denuded arterial segments with NOS inhibitor Nω-nitro-l-arginine methyl ester (l-NAME, 10− 4 M) or cyclooxygenase (COX) inhibitor indomethacin (10− 5 M) or histamine H1-receptor blocker diphenhydramine (10− 6 M), for 20 min did not inhibit the relaxation responses to morphine. Small mesenteric arterial segment contractions induced by stepwise addition of calcium to high KCl solution with no calcium were almost completely inhibited by morphine. These findings suggested that morphine-induced relaxation responses in isolated rat small mesenteric arteries were neither dependent on endothelium nor blocked by NOS or COX inhibition but they rather seem to depend on an interaction of morphine with calcium influx pathways.