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Vasorelaxing effect of U50,488H in pulmonary artery and underlying mechanism in rats
1Department of Physiology, Fourth Military Medical University, Xi'an 710032, China.
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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