Angiotensin II type 1 receptor blocker, olmesartan, restores nocturnal blood pressure decline by enhancing daytime natriuresis

Abstract

We have shown that as renal function deteriorated, night-time fall in both blood pressure and urinary sodium excretion were diminished. We have also reported that sodium intake restriction and diuretics both normalized circadian blood pressure rhythm from nondipper to dipper patterns. In this study, we investigated whether an angiotensin II receptor blocker, olmesartan, could restore night-time blood pressure fall. Twenty patients with chronic kidney disease (13 men, seven women; mean age 44.8 +/- 18.1 years; BMI 22.9 +/- 3.5 kg/m2) were studied. At baseline and 8 weeks after the treatment with olmesartan medoxomil (10-40 mg/day), 24-h blood pressure monitoring and urinary sampling for both daytime (0600-2100 h) and night-time (2100-0600 h) were repeated to compare the circadian rhythms of blood pressure and urinary sodium excretion. The 24-h mean arterial pressure was lowered by olmesartan, while urinary sodium excretion remained unchanged. On the other hand, daytime urinary sodium excretion was increased from 4.8 +/- 2.2 to 5.7 +/- 2.1 mmol/h, while night-time urinary sodium excretion tended to be reduced from 3.9 +/- 1.7 to 3.4 +/- 1.6 mmol/h. Night/day ratios of mean arterial pressure (0.98 +/- 0.1 to 0.91 +/- 0.08; P = 0.01) and urinary sodium excretion (0.93 +/- 0.5 to 0.68 +/- 0.4; P = 0.0006) were both decreased. Olmesartan enhanced night-time falls more in mean arterial pressure (r = 0.77; r2 = 0.59; P < 0.0001) and urinary sodium excretion (r = 0.59; r2 = 0.34; P = 0.007), especially in patients whose baseline night-time falls were more diminished. These findings demonstrated that olmesartan could restore night-time blood pressure fall, as seen with diuretics and sodium restriction, possibly by enhancing daytime sodium excretion. Since nocturnal blood pressure is a strong predictor of cardiovascular events, olmesartan could relieve cardiorenal load through normalization of circadian blood pressure rhythm besides having powerful ability to block the renin-angiotensin system.