Vasorelaxing effect of U50,488H in pulmonary artery and underlying mechanism in rats.

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.