Pituitary adenylate cyclase activating peptides relax human pulmonary arteries by opening of K(ATP) and K(CA) channels

Abstract

Background - Pituitary adenylate cyclase activating peptides (PACAPs) are potent endothelium independent dilators of human coronary arteries; however, their effects on human pulmonary arteries are unknown. Methods - The vasorelaxant effects of PACAP27 on human pulmonary segmental arteries were studied and the specific potassium (K+) channel regulatory mechanisms in the vasorelaxant effects were tested by means of isometric contraction experiments. Results - PACAP27 produced dose dependent relaxations of 10 μM rings preconstricted with prostaglandin F(2a) (PGF(2a)) with half maximal relaxation (IC50) at 17 nM. Pretreatment of the vessels with the ATP sensitive K+ (K(ATP)) channel blocker glibenclamide (1 μM) or with the Ca2+ activated K+ (K(Ca)) channel blocker iberiotoxin (100 nM) inhibited the PAGAP27 induced relaxation. Conclusions - These results provide evidence that PAGAPs are potent vasodilators of human pulmonary arteries and that this relaxation might be mediated by opening of K(ATP) and K(Ca) channels.