Antihypertensive Mechanism of Diuretics Based on Pressure-Natriuresis Relationship

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Abstract
Abstract We analyzed the hypotensive mechanisms of a thiazide-type diuretic, mefruside, on the basis of the pressure-natriuresis relationship. We performed a 5-week study in eight patients with essential hypertension who were given a high sodium diet (15 to 18 g NaCl per day) during the 1st and 5th weeks, a severely sodium-restricted diet (1 to 3 g/d) during the 2nd week, and a mildly sodium-restricted diet (5 to 7 g/d) during the 3rd and 4th weeks. Mefruside (25 mg/d) was administered during the 4th and 5th weeks. Urinary sodium excretion rate and mean arterial pressure were measured at the end of each week, and the pressure-natriuresis relationship was drawn by plotting urinary sodium excretion rate on the ordinate and mean arterial pressure on the abscissa before and after mefruside treatment. Before treatment, the pressure-natriuresis relationship was linear, and mean arterial pressure was changed as a consequence of sodium intake alteration (1st week, 117±9 mm Hg; 2nd week, 105±7; 3rd week, 109±9). After treatment, however, the change in mean arterial pressure was very small (4th week, 102±8 mm Hg; 5th week, 104±7). Mefruside steepened the slope of the relationship (20.8±10.5 versus 143±85 [mmol/d]/mm Hg, P <.005) without significantly shifting the x intercept (104±6 versus 101±9 mm Hg, P =NS) of the relationship. The increase in the slope was greater in patients whose slope had been depressed and blood pressure was sodium sensitive before mefruside treatment. The hypotensive effect of mefruside during a high sodium diet correlated positively with both the hypotensive effect of sodium restriction ( r =.84, P <.01) and the increase in the slope by mefruside ( r =.83, P <.02). Thus, mefruside lowers blood pressure especially in patients with high sodium sensitivity mainly by making blood pressure sodium insensitive through its diuretic action. Strict sodium restriction seems unnecessary when diuretics are administered for blood pressure control.