圧―利尿(腎機能)曲線に基づいた利尿降圧薬mefrusideの作用機序の検討

抄録

The mechanisms of the hypotensive action of a sulfonamide diuretic, mefruside (M), were analyzed based on the pressure-natriuresis relationship. A 5-week study was performed in 8 patients with uncomplicated essential hypertension, who were given a regular sodium diet (15-18 g of NaCl/day) in the 1st & 5th weeks, a severe sodium-restricted diet (2 g/day) in the 2nd week. and a mild sodium-restricted diet (7 g/day) in the 3rd & 4th weeks. M (25 mg/day) was administered in the 4 & 5th weeks. Urinary sodium excretion (UNaV) and mean arterial pressure (MAP) were measured at the end of each week, and the pressure-natriuresis curve (PNC), so-called renal function curve, was drawn by plotting UNaV on the ordinate and MAP on the abscissa before and after medication with M. The reciprocal of the slope (1/B: mmHg/mEq/day) was used for analyzing the slope (B: mEq/day/mmHg), because dietary sodium intake was altered primarily and the consequent secondary change in MAP was observed. Before medication, PNC was linear and MAP was changed in consequence of altering sodium intake (1st week: 117±9, 2nd week: 105±7, 3rd week : 109±9 mmHg). But after medication, the change in MAP was very small (4th week : 102±8, 5th week: 104±7 mmHg). M raised the slope of PNC (1/B: 0.048±0.020→0.007±0.015 mmHg/mEq/day, p<0.01), without significantly changing the x-intercept (104±6→101±9 mmHg, NS) of PNC. The rise was greater in patients whose slope had been depressed before medication of M. The hypotensive effect of M on a regular sodium diet (change in MAP from the 1st to the 5th week) correlated positively with the rise in the slope with M (r=0.833, p<0.02), but not with the leftward shift, suggesting that the effect of M is mainly due to its diuretic action, since the slope is determined by glomerulotubular balance. On the other hand, the effect of M on a mild sodium-restricted diet (change in MAP from the 3rd to the 4th weeks) did not correlated with the rise in the slope, but tended to correlate with the degree of the leftward shift of the PNC (r=0.670, p<0.10). Since the x-intercept of the PNC is determined by the renal vascular resistance, the leftward shift may be due to its vasodilating action of M. These results suggest that extreme restriction of the dietary sodium intake is not necessary under the treatment of an antihynertensive diuretic, mefruside.