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The induction of nitric oxide‐mediated relaxation of human isolated pulmonary arteries by PACAP
Author(s) -
Cardell Lars Olaf,
Hjert Ola,
Uddman Rolf
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0700992
Subject(s) - nitric oxide , medicine , cardiology , chemistry
The effects of pituitary adenylate cyclase‐activating peptide (PACAP) and vasoactive intestinal peptide (VIP) were analysed in human isolated circular segments of pulmonary arteries. Guinea‐pig pulmonary arteries were used for comparison. The responses obtained were analysed in relation to the vascular endothelium and the nitric oxide (NO) synthase inhibitor N G ‐monomethyl l ‐arginine ( l ‐NMMA). PACAP and VIP induced concentration‐dependent relaxations of precontracted pulmonary arteries. The maximal dilator response (I max ,%) and the potency (pEC 50 value) were the same for both peptides, and there were no differences in the effects obtained on human and guinea‐pig segments. PACAP and VIP were both more potent that acetylcholine (ACh). Removal of the vascular endothelium abolished the PACAP induced dilator response in pulmonary arteries from both species. The VIP induced dilatation was unaffected, whereas the response to ACh was abolished. l ‐NMMA given before PACAP inhibited the dilatation. Furthermore, l ‐NMMA also reversed the dilatation already induced by PACAP and excess concentrations of l ‐arginine restored the dilator response of the l ‐NMMA treated arteries. PACAP is a potent dilator of human pulmonary arteries. Although the dilator effect seems to be similar in amplitude to the one induced by VIP, the present results suggest differences in the underlying mechanisms of action (endothelium‐dependency) between the two peptides.British Journal of Pharmacology (1997) 120 , 1096–1100; doi: 10.1038/sj.bjp.0700992