Pilot studies with bendroflumethiazide, a recently introduced benzothiadiazine diuretic,1,2 suggested superior antihypertensive qualities. Long-term effects on outpatients were studied and compared to placebo, reserpine, and other benzothiadiazine derivatives. Our observations suggested that bendroflumethiazide, given singly, often proved unusually effective. We postulated a separate group of "diuretic sensitive" patients and a therapy-induced bimodal redistribution of blood pressure was sought. Blood pressure responsiveness was also statistically related to various other clinical parameters including dietary sodium intake. The depressor effect of low-potassium diets,3 the stimulation of aldosterone by potassium,4,5 and the results of animal experiments6,7 made it pertinent to test the blood pressure influence of potassium chloride supplementation. Overproduction of aldosterone, whatever its cause, might contribute to the refractoriness of high blood pressure to diuretic therapy. This prompted a trial of combination therapy of bendroflumethiazide with spironolactone in 17 patients with severe hypertension, inadequately controlled by bendroflumethiazide therapy alone.
GRIEBLE HG, JOHNSTON LC. Treatment of Arterial Hypertensive Disease with DiureticsI. Effects on Blood Pressure of Bendroflumethiazide, Potassium Chloride, and Spironolactone. Arch Intern Med. 1962;110(1):26–33. doi:10.1001/archinte.1962.03620190028004
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