title: Angiotensin receptor blockers shift the circadian rhythm of blood pressure by suppressing tubular sodium reabsorption.
abstract: Recently, we found that an angiotensin II receptor blocker (ARB) restored the circadian rhythm of the blood pressure (BP) from a nondipper to a dipper pattern, similar to that achieved with sodium intake restriction and diuretics (Fukuda M, Yamanaka T, Mizuno M, Motokawa M, Shirasawa Y, Miyagi S, Nishio T, Yoshida A, Kimura G. J Hypertens 26: 583-588, 2008). ARB enhanced natriuresis during the day, while BP was markedly lower during the night, resulting in the dipper pattern. In the present study, we examined whether the suppression of tubular sodium reabsorption, similar to the action of diuretics, was the mechanism by which ARB normalized the circadian BP rhythm. BP and glomerulotubular balance were compared in 41 patients with chronic kidney disease before and during ARB treatment with olmesartan once a day in the morning for 8 wk. ARB increased natriuresis (sodium excretion rate; U(Na)V) during the day (4.5 ± 2.2 to 5.5 ± 2.1 mmol/h, P = 0.002), while it had no effect during the night (4.3 ± 2.0 to 3.8 ± 1.6 mmol/h, P = 0.1). The night/day ratios of both BP and U(Na)V were decreased. The decrease in the night/day ratio of BP correlated with the increase in the daytime U(Na)V (r = 0.42, P = 0.006). Throughout the whole day, the glomerular filtration rate (P = 0.0006) and tubular sodium reabsorption (P = 0.0005) were both reduced significantly by ARB, although U(Na)V remained constant (107 ± 45 vs. 118 ± 36 mmol/day, P = 0.07). These findings indicate that the suppression of tubular sodium reabsorption, showing a resemblance to the action of diuretics, is the primary mechanism by which ARB can shift the circadian BP rhythm into a dipper pattern.
authors.affiliation: Dept. of Cardio-Renal Medicine and Hypertension, Nagoya City Univ. Graduate School of Medical Sciences, 467-8601 Nagoya, Japan. m-fukuda@med.nagoya-cu.ac.jp
authors.forename: Michio
authors.initials: M
authors.lastname: Fukuda
authors.forename: Tamaki
authors.initials: T
authors.lastname: Wakamatsu-Yamanaka
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizuno
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miura
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Tomonari
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kato
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ichikawa
authors.forename: Sota
authors.initials: S
authors.lastname: Miyagi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Shirasawa
authors.forename: Akinori
authors.initials: A
authors.lastname: Ito
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Yoshida
authors.forename: Genjiro
authors.initials: G
authors.lastname: Kimura
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D057912:Angiotensin II Type 2 Receptor Blockers / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D002940:Circadian Rhythm / Q000187:drug effects*; D003404:Creatinine / Q000652:urine; D005260:Female; D060730:Glomerular Filtration Barrier / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007674:Kidney Diseases / Q000378:metabolism; D007677:Kidney Function Tests; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects; D012964:Sodium / Q000378:metabolism* / Q000652:urine; D013777:Tetrazoles / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D057912:Angiotensin II Type 2 Receptor Blockers; D007093:Imidazoles; D013777:Tetrazoles; C437965:olmesartan; D012964:Sodium; D003404:Creatinine