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Pituitary adenylate cyclase activating peptides relax humanpulmonary arteries by opening of KATP and KCachannels |
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| Authors: | L. Bruch S. Rubel A. Kastner K. Gellert M. Gollasch C. Witt |
| Affiliation: | Department of Internal Medicine I, Charité University Hospital, Humboldt University of Berlin, Germany. |
| Abstract: | BACKGROUND—Pituitaryadenylate cyclase activating peptides (PACAPs) are potent endotheliumindependent dilators of human coronary arteries; however, their effectson human pulmonary arteries are unknown. Methods—Thevasorelaxant effects of PACAP27 on human pulmonary segmental arterieswere studied and the specific potassium (K+) channelregulatory mechanisms in the vasorelaxant effects were tested by meansof isometric contraction experiments. RESULTS—PACAP27produced dose dependent relaxations of 10 µM rings preconstrictedwith prostaglandin F2α (PGF2α ) with half maximal relaxation (IC50) at 17 nM. Pretreatment of thevessels with the ATP sensitive K+ (KATP)channel blocker glibenclamide (1 µM) or with the Ca2+activated K+ (KCa) channel blockeriberiotoxin (100 nM) inhibited the PACAP27 induced relaxation. Conclusions—Theseresults provide evidence that PACAPs are potent vasodilators of humanpulmonary arteries and that this relaxation might be mediated byopening of KATP and KCa channels. |
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