REN and Hypertension resistant to conventional therapy: The results of the PATHWAY-2 mechanisms substudies show that the efficacy of spironolactone as an antihypertensive drug could be anticipated from our findings that resistant hypertension is a salt-retaining condition, associated with high aldosterone-to-renin ratios, and that spironolactone was substantially superior to the other standard antihypertensive drugs in reducing indices of salt and water retention—ie, it was reducing blood pressure primarily via diuretic actions.