AMILORIDE ANALOGS CAUSE ENDOTHELIUM-DEPENDENT RELAXATION IN THE CANINE CORONARY-ARTERY INVITRO - 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 arteri..