Pituitary adenylate cyclase activating peptides relax human pulmonary arteries by opening of KATP and KCa channels

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 mu M rings preconstricted with prostaglandin F-2 alpha (PGF(2 alpha)) with half maximal relaxation (IC50) at 17 nM. Pretreatment of the vessels with the ATP sensitive K+ (K-ATP) channel blocker glibenclamide (1 mu M) or with the Ca2+ activated K+ (K-Ca) channel blocker iberiotoxin (100 nM) inhibited the PACAP27 induced relaxation. Conclusions-These results provide evidence that PACAPs are potent vasodilators of human pulmonary arteries and that this relaxation might be mediated by opening of K-ATP and K-Ca channels.