Pituitary adenylate cyclase activating peptides relax human pulmonary arteries by opening of KATP and KCachannels
- aDepartment of Internal Medicine I, bDepartment of Surgery, cFranz Volhard Clinic and Max Delbrück Center for Molecular Medicine, dCharité University Hospitals, Humboldt University of Berlin, Germany
- Dr C Witt, Humboldt University Berlin, Charité I, Medical Clinic, Schumannstrasse 20/21, D-10098 Berlin, Germany.
- Received 30 June 1997
- Revision requested 31 July 1997
- Revised 27 February 1998
- Accepted 30 March 1998
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 F2α (PGF2α ) 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.
