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 microM rings preconstricted with prostaglandin F2 alpha (PGF2 alpha) with half maximal relaxation (IC50) at 17 nM. Pretreatment of the vessels with the ATP sensitive K+ (KATP) channel blocker glibenclamide (1 microM) 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.
Bruch
L
L
Department of Internal Medicine I, Charité University Hospital, Humboldt University of Berlin, Germany.
Rubel
S
S
Kästner
A
A
Gellert
K
K
Gollasch
M
M
Witt
C
C
D000704:Analysis of Variance; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects*; D009479:Neuropeptides / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects*; D011651:Pulmonary Artery / Q000187:drug effects*; D012044:Regression Analysis; D018709:Statistics, Nonparametric; D014665:Vasodilator Agents / Q000494:pharmacology*
C495401:ADCYAP1 protein, human; D007004:Hypoglycemic Agents; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D010455:Peptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014665:Vasodilator Agents; C064719:iberiotoxin; D005905:Glyburide