title: Amiloride analogues cause endothelium-dependent relaxation in the canine coronary artery in vitro: possible role of Na+/Ca2+ exchange.
abstract: 1. A number of amiloride analogues were used to test the proposal that Na+/Ca2+ 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+/Ca2+ and Na+/H+ exchange whilst the latter block the Na+ channel and the Na+/Ca2+ exchange. 2. Both series of compounds caused relaxation in isolated rings of dog coronary artery (EC50 values, 1-10 microM) presumably due to release of EDRF since removal of endothelium greatly attenuated the response. 3. Amiloride (1-100 microM) 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+/Ca2+ exchange operating in the forward mode to extrude Ca2+. This mechanism may be important in the control of EDRF release.
authors.affiliation: Baker Medical Research Institute, Victoria, Australia.
authors.forename: T M
authors.initials: TM
authors.lastname: Cocks
authors.forename: P J
authors.initials: PJ
authors.lastname: Little
authors.forename: J A
authors.initials: JA
authors.lastname: Angus
authors.forename: E J
authors.initials: EJ
authors.lastname: Cragoe
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D003331:Coronary Vessels / Q000378:metabolism; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide; D012964:Sodium / Q000378:metabolism; D014303:Trinitrotoluene / Q000494:pharmacology
chemical_list: D001685:Biological Factors; D014303:Trinitrotoluene; D009569:Nitric Oxide; D000001:Calcimycin; D000584:Amiloride; D012964:Sodium; D002118:Calcium