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Amiloride analogues cause endothelium‐dependent relaxation in the canine coronary artery in vitro : possible role of Na + /Ca 2+ exchange
Author(s) -
Cocks T.M.,
Little P.J.,
Angus J.A.,
Cragoe E.J.
Publication year - 1988
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 - 10.1111/j.1476-5381.1988.tb16549.x
Subject(s) - amiloride , endothelium derived relaxing factor , chemistry , endothelium , biophysics , in vitro , stereochemistry , pharmacology , sodium , medicine , biochemistry , biology , organic chemistry
1 A number of amiloride analogues were used to test the proposal that Na + /Ca 2+ exchange may play a role in the secretion of endothelium‐derived relaxing factor (EDRF). The analogues used were those substituted on either the 5‐amino group or the terminal guanidino nitrogen atom. The former block both Na + /Ca 2+ and Na + /H + exchange whilst the latter block the Na + channel and the Na + /Ca 2+ exchange. 2 Both series of compounds caused relaxation in isolated rings of dog coronary artery (EC 50 values, 1–10 μ M ) presumably due to release of EDRF since removal of endothelium greatly attenuated the response. 3 Amiloride (1–100 μ M ) had little effect on either endothelium‐intact or denuded arteries. 4 The guanidino substituted analogues also appeared to block selectively the relaxation response to acetylcholine in the coronary artery, independently of their EDRF‐releasing activity. 5 It is proposed that endothelial cells have an active Na + /Ca 2+ exchange operating in the forward mode to extrude Ca 2+ . This mechanism may be important in the control of EDRF release.