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
相关论文
共 34 条
  • [1] ROLE OF NITRIC-OXIDE IN ADENOSINE RECEPTOR-MEDIATED RELAXATION OF PORCINE CORONARY-ARTERY
    ABEBE, W
    HUSSAIN, T
    OLANREWAJU, H
    MUSTAFA, SJ
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1995, 269 (05): : H1672 - H1678
  • [2] ROLE OF NITRIC-OXIDE AND CAMP IN PROSTAGLANDIN-INDUCED PIAL ARTERIAL VASODILATION
    ARMSTEAD, WM
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1995, 268 (04): : H1436 - H1440
  • [3] EVIDENCE THAT PROSTAGLANDINS I-2, E(2), AND D-2 MAY ACTIVATE ATP-SENSITIVE POTASSIUM CHANNELS IN THE ISOLATED RAT-HEART
    BOUCHARD, JF
    DUMONT, E
    LAMONTAGNE, D
    [J]. CARDIOVASCULAR RESEARCH, 1994, 28 (06) : 901 - 905
  • [4] Adenosine A(1) and A(2) receptors mediate tone-dependent responses in feline pulmonary vascular bed
    Cheng, DY
    DeWitt, BJ
    Suzuki, F
    Neely, CF
    Kadowitz, PJ
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1996, 270 (01): : H200 - H207
  • [5] COLEMAN RA, 1994, PHARMACOL REV, V46, P205
  • [6] ADENOSINE RECEPTOR-MEDIATED CORONARY-ARTERY RELAXATION AND CYCLIC-NUCLEOTIDE PRODUCTION
    CUSHING, DJ
    BROWN, GL
    SABOUNI, MH
    MUSTAFA, SJ
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1991, 261 (02): : H343 - H348
  • [7] EFFECTS OF PGE(1) IN EXPERIMENTAL VASOCONSTRICTIVE PULMONARY-HYPERTENSION
    DAGHER, E
    DUMONT, L
    CHARTRAND, C
    BLAISE, G
    [J]. EUROPEAN SURGICAL RESEARCH, 1993, 25 (02) : 65 - 73
  • [8] Comparison of the effects of nicorandil, pinacidil and nitroglycerin on hypoxic and hypercapnic pulmonary vasoconstriction in the isolated perfused lung of rat
    Dumas, M
    Dumas, JP
    Rochette, L
    Advenier, C
    Giudicelli, JF
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 1996, 117 (04) : 633 - 638
  • [9] HYPOXIA MODIFIES THE VASODILATORY EFFECTS OF NITROGLYCERIN, PROSTAGLANDIN E(1), AND HYDRALAZINE ON ISOLATED PORCINE CORONARY-ARTERIES
    FUKUDA, S
    SAKUMA, K
    TSUKUI, A
    FUJIWARA, N
    TANAKA, T
    FUJIHARA, H
    TORIUMI, T
    SHIMOJI, K
    [J]. JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1994, 23 (05) : 852 - 858
  • [10] FUKUDA S, 1992, J PHARMACOL EXP THER, V2600, P1128