EFFECT OF SODIUM-TRANSPORT INHIBITORS ON AIRWAY SMOOTH-MUSCLE CONTRACTILITY INVITRO

被引:27
作者
KNOX, AJ
AJAO, P
BRITTON, JR
TATTERSFIELD, AE
机构
[1] Respiratory Medicine Unit, City Hospital, Nottingham NG5 1PB, Hucknall Road
关键词
Airway smooth muscle; Amiloride; Ouabain; Sodium;
D O I
10.1042/cs0790315
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
1. To determine whether alterations in membrane sodium transport in airway smooth muscle can alter its contractility, we studied the effect of ouabain (a Na+/K+-adenosine triphosphatase inhibitor) and amiloride on contractile responses in bovine trachea and human bronchial rings in a series of studies. 2. Ouabain (10-6-10-4 mol/l) caused concentration-related contraction of bovine trachea with a maximum effect at 30 min; the mean increases in tension with 10-6, 10-5 and 10-4 mol/l ouabain were 19, 27, and 32%, respectively, of the maximum response seen with 10-3 mol/l histamine (n = 6). In human bronchial rings, ouabain (10-5 mol/l) caused a mean contraction which was 40% of the maximum response to methacholine (n = 8). 3. Calcium-free fluid (plus ethylenediaminetetra-acetic acid) and nifedipine (10-5 mol/l) inhibited ouabain-induced contractions, suggesting that contraction was mediated in part by calcium entry via voltage-dependent calcium channels. Phentolamine (10-5 ml/l) was without effect. 4. Ouabain (10-5 mol/l) did not alter histamine responsiveness in bovine trachea or methacholine responsiveness in human bronchial rings. 5. Amiloride did not affect resting tone in bovine trachea but caused a concentration-dependent relaxation of bovine tracheal strips preconstricted with carbachol, 10-3 mol/l amiloride relaxing strips completely over 15 minutes (n = 8). Pretreatment with amiloride significantly inhibited contraction produced by both histamine and carbachol in a dose-related manner, 10-5, 10-4 and 10-3 mol/l amiloride shifting the concentration of histamine producing 50% maximal contraction by 3-, 8- and 35-fold (n = 10) and that of carbachol by 1.4-, 6- and 86-fold (n = 8), respectively. 6. Amiloride also reduced the contraction produced by 10-4 mol/l ouabain from 32% (control) to 7% of the maximum histamine response. 7. Our results suggest that alterations in cell membrane sodium transport modify the contractile properties of airway smooth muscle.
引用
收藏
页码:315 / 323
页数:9
相关论文
共 37 条
  • [1] AIRWAY RESPONSES TO INHALED OUABAIN AND HISTAMINE IN CONSCIOUS GUINEA-PIGS
    AGRAWAL, KP
    HYATT, RE
    [J]. JOURNAL OF APPLIED PHYSIOLOGY, 1986, 60 (06) : 2089 - 2093
  • [2] BATEMAN CJ, 1986, CLIN SCI, V70, pP65
  • [3] AMILORIDE - A MOLECULAR PROBE OF SODIUM-TRANSPORT IN TISSUES AND CELLS
    BENOS, DJ
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1982, 242 (03): : C131 - C145
  • [4] BESTERMAN JM, 1985, J BIOL CHEM, V260, P1155
  • [5] COMPETITIVE INTERACTION OF AMILORIDE AND VERAPAMIL WITH ALPHA-1-ADRENOCEPTORS IN VASCULAR SMOOTH-MUSCLE
    BHALLA, RC
    SHARMA, RV
    [J]. JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1986, 8 (05) : 927 - 932
  • [6] MECHANISMS OF ACTION OF TRANSMITTERS AND OTHER SUBSTANCES ON SMOOTH-MUSCLE
    BOLTON, TB
    [J]. PHYSIOLOGICAL REVIEWS, 1979, 59 (03) : 606 - 718
  • [7] NA-CA EXCHANGE IN VASCULAR SMOOTH-MUSCLE
    BRADING, AF
    LATEGAN, TW
    [J]. JOURNAL OF HYPERTENSION, 1985, 3 (02) : 109 - 116
  • [8] BROEKAERT A, 1973, ARCH INT PHARMACOD T, V203, P393
  • [9] BULLOCK CG, 1981, J PHYSIOL-LONDON, V318, pP46
  • [10] EFFECT OF CHANGING DIETARY-SODIUM ON THE AIRWAY RESPONSE TO HISTAMINE
    BURNEY, PGJ
    NEILD, JE
    TWORT, CHC
    CHINN, S
    JONES, TD
    MITCHELL, WD
    BATEMAN, C
    CAMERON, IR
    [J]. THORAX, 1989, 44 (01) : 36 - 41