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Thorax 1998;53:586-587 ( July )

Short paper

Pituitary adenylate cyclase activating peptides relax human pulmonary arteries by opening of KATP and KCa channels Leonhard Bruch,a Susann Rubel,a Andrea Kästner,a Klaus Gellert,b Maik Gollasch,c Christian Witta

a Department of Internal Medicine I, b Department of Surgery, c Franz Volhard Clinic and Max Delbrück Center for Molecular Medicine, d Charité University Hospitals, Humboldt University of Berlin, Germany

Correspondence to: Dr C Witt, Humboldt University Berlin, Charité I, Medical Clinic, Schumannstrasse 20/21, D-10098 Berlin, Germany.

Received 30 June 1997; Returned to authors 31 July 1997; Revised version received 27 February 1998; Accepted for publication 30 March 1998

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 F2alpha (PGF2alpha ) with half maximal relaxation (IC50) at 17 nM. Pretreatment of the vessels with the ATP sensitive K+ (KATP) channel blocker glibenclamide (1 µM) or with the Ca2+ activated K+ (KCa) 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 KATP and KCa channels.

Keywords: PACAP; potassium channel opener; Ca sparks; human pulmonary artery

© 1998 by Thorax


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