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Role of potassium channels and nitric oxide in the effects of iloprost and prostaglandin E 1 on hypoxic vasoconstriction in the isolated perfused lung of the rat
Author(s) -
Dumas Monique,
Dumas JeanPaul,
Rochette Luc,
Advenier Charles,
Giudicelli JeanFrançois
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.0700912
Subject(s) - iloprost , forskolin , glibenclamide , prostacyclin , adenosine , chemistry , nitric oxide , medicine , endocrinology , cromakalim , pharmacology , anesthesia , receptor , diabetes mellitus
1 The aims of this study were to compare in the rat isolated perfused lung preparation, the antagonist effects of iloprost, a stable analogue of prostacyclin, and prostaglandin E 1 (PGE 1 ) on the hypoxic pulmonary pressure response, and to investigate the possible involvement of K ATP and K Ca channels and of EDRF (NO) in these effects. In addition, iloprost and PGE 1 effects were compared to those of adenosine and forskolin. 2 Isolated lungs from male Wistar rats (260–320 g) were ventilated with 21% O 2 + 5% CO 2 + 74% N 2 (normoxia) or 5% CO 2 + 95% N 2 (hypoxia) and perfused with a salt solution supplemented with ficoll. Glibenclamide (1 μm), charybdotoxin (0.1 μm), N G ‐nitro‐L‐arginine methyl ester (l‐NAME, 100 μm) were used to block K ATP , K Ca channels and NO synthesis, respectively. 3 Iloprost, PGE 1 , adenosine and forskolin caused relaxation during the hypoxic pressure response. The order of potency was: iloprost > PGE 1 = forskolin > adenosine. EC 50 values were 1.91 ± 0.52 10 −9 M, 3.31 ± 0.58 10 −7 M, 3.24 ± 0.78 10 −7 M and 7.70 ± 1.68 10 −5 M, respectively. Glibenclamide, charybdotoxin and L‐NAME inhibited partially the relaxant effects of iloprost and forskolin but not those of PGE 1 . 4 It is concluded that in the rat isolated lung preparation, iloprost and forskolin but not PGE 1 dilate pulmonary vessels partly through K ATP channels, K Ca channels and nitric oxide release. Furthermore our results suggest that the role of cyclic AMP in these effects is not unequivocal.