In 79 patients with essential hypertension, treatment with propranolol hydrochloride and chlorthalidone together produced significantly greater falls in both systolic and diastolic blood pressures than were obtained with either drug alone. There were no differences between patients in the high, normal, and low renin subgroups in their responsiveness to this combination. Although plasma renin level during combined treatment was twice as high as it was in the untreated control, aldosterone excretion actually decreased. These divergent changes may have been influenced by the renin-raising and aldosterone-lowering effects of the marked hypokalemia observed during combined treatment. By comparison with patients whose blood pressures fell, treatment in nonresponding patients produced even greater body weight reductions and significantly higher renin and aldosterone values. It is possible that increased activity of the renin axis, triggered by excessive volume depletion and perhaps by changes in potassium balance, were responsible for sustaining the high levels of blood pressure in those patients failing to respond to treatment.
(Arch Intern Med 137:284-289, 1977)