Letter by Angus and Wright Regarding Article, “Pannexin-1 Channels as an Unexpected New Target of the Antihypertensive Drug Spironolactone”

We have read with interest the recent article by Good et al1 on the additional role of the antihypertensive drug spironolactone and also the accompanying editorial by Huke.2 Good et al1 propose that spironolactone at therapeutic plasma concentrations inhibits small artery smooth muscle cell pannexin-1 (Panx-1) channels preventing the action of α1-adrenoceptor–mediated vasoconstriction. This novel action would add to the well-accepted mechanism of action of spironolactone as an antagonist of mineralocorticoid receptors to lower blood pressure.This work builds on a paper from the same laboratory that originally reported that the antimalarial drug mefloquine selectively inhibited α1-adrenoceptor–mediated contraction of small arteries via inhibition of Panx-1 channels.3 Their proposed mechanism was that Panx-1 channels located on smooth muscle cells of small arteries, when open, allow the release of ATP that acts autocrine-like back on ATP P2X1 receptors that finally contract the smooth muscle.3We have published a series of articles addressing this novel pannexin/ATP mechanism that is …