Dept. of Cardio-Renal Medicine and Hypertension, Nagoya City Univ. Graduate School of Medical Sciences, 467-8601 Nagoya, Japan.
Am J Physiol Renal Physiol. 2011 Nov;301(5):F953-7. doi: 10.1152/ajprenal.00167.2011. Epub 2011 Aug 24.
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.
最近，我们发现血管紧张素 II 受体阻滞剂（ARB）可将非杓型血压（BP）节律恢复至杓型，作用类似于钠摄入限制和利尿剂（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 增强了白天的排钠作用，同时夜间血压明显降低，导致杓型模式。在本研究中，我们研究了 ARB 是否通过抑制肾小管钠重吸收来发挥作用，类似于利尿剂的作用，从而使血压的昼夜节律恢复正常。在接受奥美沙坦治疗 8 周期间，我们比较了 41 例慢性肾脏病患者的血压和肾小球-肾小管平衡。ARB 增加了白天的排钠作用（钠排泄率；U(Na)V）（4.5 ± 2.2 至 5.5 ± 2.1 mmol/h，P = 0.002），但夜间无作用（4.3 ± 2.0 至 3.8 ± 1.6 mmol/h，P = 0.1）。BP 和 U(Na)V 的夜间/日间比值均降低。BP 和 U(Na)V 的夜间/日间比值降低与白天 U(Na)V 的增加呈负相关（r = 0.42，P = 0.006）。全天，ARB 显著降低肾小球滤过率（P = 0.0006）和肾小管钠重吸收（P = 0.0005），尽管 U(Na)V 保持不变（107 ± 45 与 118 ± 36 mmol/day，P = 0.07）。这些发现表明，ARB 可以将血压的昼夜节律转变为杓型模式，其主要机制是抑制肾小管钠重吸收，作用类似于利尿剂。
