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...Continue Reading
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