The renin response to diuretic therapyl A limitation of antihypertensive potential.

We attempted to determine whether a diuretic-induced increase in renin secretion results in angiotensin II-mediated vasoconstriction which counteracts the antihypertensive action of diuretics.The angiotensui antagonist saralasin was administered to nine normal renin and five low renin essential hypertensives prior to and during stimulation of the renin-angiotendn system by 6 weeks of chronic diuretic therapy alone.Initial responses to saralasin infusion in all subjects on placebo varied, but were pressor overall.Following chronic polythiazide therapy, saralasin induced depressor responses of variable magnitude in seven of nine normal renin subjects.The combination of the diuretic and saralasin normalized blood pressure in four subjects.However, four normal renin subjects maintained a diastolic Mood pressure greater than 95 mm Hg despite simultaneous volume depletion and angiotensin blockade.One had a maximum antihypertensive effect with diuretic therapy alone.Pressor responses to saralasin persisted in four of five low renin subjects despite diuretic therapy.In general, the magnitude of the change hi plasma renin activity induced by diuretic therapy correlated with the difference in Mood pressure responses to saralasin.However, individual Mood pressure responses and absolute renin levels after diuretic therapy failed to predict consistently the ensuing responses to saralasin.Hence, in eight subjects (seven normal and one low renin), the compensatory increase in renin secretion hi response to diuretic-induced volume depletion limited diuretic antihypertensive efficacy.Yet diuretic-induced angiotensin dependency was not the sole mechanism supporting residual hypertension hi all subjects refractory to diuretic therapy.