Influence of two doses of irbesartan on non-dipper circadian blood pressure rhythm in salt-sensitive black hypertensives under high salt diet.
The authors examined whether the blockage of angiotensin II receptors by irbesartan (IRB) can reverse the "non-dipper" circadian rhythm of blood pressure (BP) to a "dipper" pattern in black salt-sensitive hypertensive patients submitted to a high-sodium loading. Twelve black salt-sensitive hypertensive patients (seven men; age, 35-58 years) on a high-sodium diet (300 mmol Na+ per day) were followed for 8 weeks. A placebo was given during the first 2 weeks, followed by 2 weeks on IRB 150 mg/d, 2 weeks on placebo, and 2 weeks on IRB 300 mg/d. On the last day of placebo, IRB 150 mg/d, and IRB 300 mg/d treatments, 24-hour BP and urinary 24-hour excretion of Na+ and potassium were measured. On placebo, ambulatory mean arterial pressure (MAP) was 112 mm Hg+/-2 (24 h), 112 mm Hg+/-2 (daytime), and 111 mm Hg+/-2 (nighttime), showing a clear circadian non-dipper profile. Versus placebo, IRB 150 mg/d reduced MAP by 4.2 mm Hg+/-1.1 (24 h), 2.6 mm Hg+/-0.8 (daytime) and 6.0 mm Hg+/-1.3 (nighttime; P<0.05 vs. placebo) and IRB 300 mg/d reduced MAP by 7.8 mm Hg+/-1.4 (24 h), 3.9 mm Hg+/-1.1 (daytime), and 11.8 mm Hg+/-2.1 mm Hg (all P<0.02 vs. placebo); nighttime/daytime MAP decrease was 0.7+/-0.8% on placebo, 3.5+/-2.1% on IRB 150 mg/d, and 7.0+/-1.2% on IRB 300 mg/d (P<0.02 for trend). Compared with placebo, IRB significantly increased serum potassium and plasma renin activity and reduced fractional excretion of potassium and plasma aldosterone levels in a dose-dependent manner. Body weight and urinary sodium excretion did not change throughout the study. It was concluded that the angiotensin receptor blocker IRB can reverse the BP non-dipper profile in salt-sensitive hypertensive patients on a high-salt diet, restoring nocturnal BP decline by a predominantly dose-dependent reduction of nighttime BP. Although the increment of potassium balance and reduction of aldosterone may account for this effect, it occurs independently of increased natriuresis. It is speculated that blunting of nighttime BP decrease in black salt-sensitive hypertensive patients may be related to a deficient suppression of the renin-angiotensin system during the night.
Polónia
Jorge
J
Clinical Pharmacology Unit, Faculdade de Medicina do Porto, Portugal. jjpolonia@mail.telepac.pt
Diogo
Domingos
D
Caupers
Paula
P
Damasceno
Albertino
A
D000328:Adult; D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D044383:Black People; D001794:Blood Pressure / Q000187:drug effects*; D002940:Circadian Rhythm; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D013777:Tetrazoles / Q000008:administration & dosage / Q000627:therapeutic use*
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D017673:Sodium Chloride, Dietary; D013777:Tetrazoles; D000077405:Irbesartan