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

被引:24
作者
Dumas, M
Dumas, JP
Rochette, L
Advenier, C
Giudicelli, JF
机构
[1] UNIV PARIS 05,PHARMACOL LAB,F-75270 PARIS,FRANCE
[2] FAC MED PARIS SUD,DEPT PHARMACOL,F-94276 LE KREMLIN BICETR,FRANCE
关键词
hypoxic pulmonary vasoconstriction; rat isolated perfused lung; iloprost; prostaglandin El; nitric oxide; K-ATP channels; K-Ca channels;
D O I
10.1038/sj.bjp.0700912
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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% CO2+74% N-2 (normoxia) or 5% CO2+95% N-2 (hypoxia) and perfused with a salt solution supplemented with ficoll. Glibenclamide (1 mu M), charybdotoxin (0.1 mu M), N-G-nitro-L-arginine methyl ester (L-NAME, 100 mu M) 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.
引用
收藏
页码:405 / 410
页数:6
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