Causes of inadequate response to antihypertensive drugs. Volume factors.

Diuretic therapy, by producing a negative salt and water balance, eliminates the false tolerance to sympatholytic drugs that often occurs during long-term monotherapy. This tolerance results from salt and water retention produced by the drugs. Review of published results suggests a primacy for arterial pressure reduction in this fluid because suppressed renal sympathetic activity should facilitate salt and water excretion through lessened alpha-adrenergic influence on tubular reabsorption, and beta-adrenergic inhibition would diminish renin release thus promoting natriuresis. The return of hypertension that characterizes the false tolerances seems paradoxical because these drugs cause venodilation, which should provide ample storage of expanded blood volume without affecting cardiac output. However, animal studies have suggested that dilated veins have decreased compliance; if that is so, in humans it would mean that fluid retention would be accompanied by a redistribution of blood into the central circulation, with a rise in cardiac output.