The renin-aldosterone system in low-dose chlorothiazide treatment of hypertensive subjects

Eight patients with essential hypertension were treated with chlorothizide 250 mg daily for 4 weeks with 500 mg daily for further 8 weeks. Both systolic and diastolic blood pressures (BP) decreased significantly during the lower dosage (p < 0.05). Only the diastolic BP continued decrease during the higher dosage regimen of chlorothiazide (p < 0.05). Plasma renin activity (PRA) and plasma aldosterone (PA) did not increase during the lower dosage of chlorothiazide. During 4 weeks on the dosage of 500 mg of chlorothiazide daily, PRA increased by 79 per cent (p < 0.001) and PA by 66 per cent (p < 0.001) from the level of the lower dosage. During the next 4 weeks, no changes in PRA or PA were seen. The result shows the strong compensatory activation renin-aldosterone system on the usual chlorothiazide therapy. In spite of a decrease in BP, the lower dosage was not accompanied with any significant compensation. Renin-aldosterone system during diuretic therapy not only causes the so-called false tolerance to antihypertensive effect, but also potentiates the loss of potassium. This can best be avoided by using the minimal effective dosage of the diuretic drug.