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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 …