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PubMed1996

Antihypertensive mechanism of diuretics based on pressure-natriuresis relationship.

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.

Aged↗
PubMed1977

Haemodynamic effects of saluretic treatment and beta-receptor blockade in patients with essential hypertension.

The long-term haemodynamic effects of treatment with mefruside alone or in combination with alprenolol have been studied in nine patients with essential hypertension. After four months of mefruside therapy alone there was a significant decrease in intraarterial BP both at rest and during standardized leg exercise. Cardiac output and calculated total peripheral vascular resistance (TPVR) showed only minor mean decreases which were not statistically significant. Stroke volume tended to decrease and heart rate to increase. After another four months' treatment with addition of alprenolol there was a further significant decrease in intraarterial BP, related mainly to a further mean decrease in cardiac output which was not statistically significant. Heart rate decreased significantly, stroke volume was not significantly changed. Compared with the pretreatment levels, combination therapy induced a substantial decrease in intraarterial BP and a significant decrease in cardiac output both at rest in supine position and during standardized leg exercise. TPVR decreased slightly both at rest and during exercise but the change was not statistically significant. The results suggest that the decrease in BP after combined therapy with mefruside and alprenolol is mainly related to a decrease in cardiac output, the changes in TPVR being not significant. The additive hypotensive effect of alprenolol seems to be related in part to blocking of the increase in sympathetic activity that was found after treatment with mefruside alone.

Adult↗