“…It was at first assumed that these drugs were hypotensive in man by consequence of their diuretic action because the initial fall in the resting blood pressure of hypertensive patients was accompanied by reduction in plasma volume, cardiac output and plasma concentration of sodium (Freis, Wanko, Wilson & Parrish, 1958;Fuchs, Moyer & Newman, 1960). After approximately 5 days of continuous therapy with a benzothiadiazine, however, refractoriness to the diuretic effect develops; plasma volume, cardiac output and plasma electrolytes are restored, but the hypotensive action remains (Gifford, Mattox, Orvis, Sones & Rosenvear, 1961;Talso & Carballo, 1960;Freis et al, 1958;Fuchs et al, 1960;Conway & Lauwers, 1961). The similarity of the diuretic effects of these compounds in normal and hypertensive patients (Hollander, Chobanian & Wilkins, 1960) contrasts with their ability to lower the blood pressure solely in the hypertensives (Freis et al, 1958;Friedman, Nakashima & Friedman, 1960) and again stresses the dissociation of these two actions.…”