PITUITARY ADENYLATE-CYCLASE ACTIVATING PEPTIDES RELAX HUMAN PULMONARY-ARTERIES BY OPENING OF K-ATP AND K-CA CHANNELS

Background-Pituitary adenylate cyclase activating peptides (PACAPs) ar e potent endothelium independent dilators of human coronary arteries; however, their effects on human pulmonary arteries are unknown. Method s-The vasorelaxant effects of PACAP27 on human pulmonary segmental art eries were studied and the specific potassium (K+) channel regulatory mechanisms in the vasorelaxant effects were tested by means of isometr ic contraction experiments. Results-PACAP27 produced dose dependent re laxations of 10 mu M rings preconstricted with prostaglandin F-2 alpha (PGF(2 alpha)) with half maximal relaxation (IC50) at 17 nM. Pretreat ment 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 bl ocker iberiotoxin (100 nM) inhibited the PACAP27 induced relaxation.Co nclusions-These results provide evidence that PACAPs are potent vasodi lators of human pulmonary arteries and that this relaxation might be m ediated by opening of K-ATP and K-Ca channels.