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  • Title: Vasorelaxing effect of U50,488H in pulmonary artery and underlying mechanism in rats.
    Author: Sun X, Ma S, Zang YM, Lu SY, Guo HT, Bi H, Wang YM, Ma H, Ma XL, Pei JM.
    Journal: Life Sci; 2006 Apr 18; 78(21):2516-22. PubMed ID: 16336977.
    Abstract:
    AIM: To investigate the relaxation effect and underlying mechanism of U50,488H (a selective kappa-opioid receptor agonist) in pulmonary artery in the rat. METHODS: Isolated pulmonary artery ring was perfused and the tension of the vessel was measured. RESULTS: U50,488H relaxed the pulmonary artery ring in a dose-dependent manner and the effect was abolished by nor-binaltorphimine, a selective kappa-opioid receptor antagonist. The relaxation effect of U50,488H in pulmonary artery was partially endothelium-dependent and was significantly attenuated in the presence of L-NAME. The relaxation effect of U50,488H was significantly attenuated by K(V) channel blocker 4-AP (4-aminopyridine), but not by glibenclamide (ATP-sensitive K+ channel blocker) nor TEA (tetraethylamonium, Ca2+-activated K+ channel blocker). Further study also showed that endothelium denudation and 4-AP have an additive inhibitory effect on pulmonary artery relaxation caused by U50,488H. CONCLUSION: Kappa-opioid receptor activation by U50,488H relaxes pulmonary artery via two separate pathways: one is endothelium-derived nitric oxide, the other is K(V) channel in pulmonary artery smooth muscle.
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