Role of potassium channels and nitric oxide in the effects of iloprost and prostaglandin E1 on hypoxic vasoconstriction in the isolated perfused lung of the rat.
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 E1 (PGE1) on the hypoxic pulmonary pressure response, and to investigate the possible involvement of KATP and KCa channels and of EDRF (NO) in the effects. In addition, iloprost and PGE1 effects were compared to those of adenosine and forskolin. 2. Isolated lungs from male Wistar rats (260-320 g) were ventilated with 21% O2 + 5% CO2 + 74% N2 (normoxia) or 5% CO2 + 95% N2 (hypoxia) and perfused with a salt solution supplemented with ficoll. Glibenclamide (1 microM), charybdotoxin (0.1 microM), NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) were used to block KATP, KCa channels and NO synthesis, respectively. 3. Iloprost, PGE1, adenosine and forskolin caused relaxation during the hypoxic pressure response. The order of potency was: iloprost > PGE1 = forskolin > adenosine. EC50 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 PGE1. 4. It is concluded that in the rat isolated lung preparation, iloprost and forskolin but not PGE1 dilate pulmonary vessels partly through KATP channels, KCa and nitric oxide release. Furthermore our results suggest that the role of cycli AMP in these effects is not unequivocal.
Dumas
M
M
Laboratoire de Physiopathologie et de Pharmacologie Cardiovasculaires Expérimentales, Faculté de Médecine, Dijon, France.
Dumas
J P
JP
Rochette
L
L
Advenier
C
C
Giudicelli
J F
JF
D000241:Adenosine / Q000494:pharmacology; D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D016285:Iloprost / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D015221:Potassium Channels; D014665:Vasodilator Agents; D005576:Colforsin; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000527:Alprostadil; D016285:Iloprost; D000241:Adenosine; D019331:NG-Nitroarginine Methyl Ester