Yukako Isobe‐Sasaki 1 , Michio Fukuda , 1 , Yoshiaki Ogiyama 1 , Ryo Sato 1 , Toshiyuki Miura 1 , Daisuke Fuwa 1 , Masashi Mizuno 1 , Tetsuhei Matsuoka 1 , Hiroko Shibata 1 , Hiroyuki Ito 1 , Minamo Ono 1 , Sumiko Abe‐Dohmae 2 , Ken Kiyono 3 , Yoshiharu Yamamoto 4 , Hiroyuki Kobori 5 , Makoto Michikawa 2 , Junichiro Hayano 6 , Nobuyuki Ohte 1
02 June 2017
We have revealed that even in humans, activated intrarenal renin–angiotensin–aldosterone system ( RAAS) enhances tubular sodium reabsorption to facilitate salt sensitivity and nondipper rhythm of blood pressure ( BP), and that angiotensin receptor blocker ( ARB) could increase daytime urinary sodium excretion rate ( U N aV) to produce lower sodium balance and restore nondipper rhythm. However, the sympathetic nervous system and intrarenal dopaminergic system can also contribute to renal sodium handling. A total of 20 patients with chronic kidney disease (61 ± 15 years) underwent 24‐h ambulatory BP monitoring before and during two‐day treatment with ARB, azilsartan. Urinary angiotensinogen excretion rate ( U AGTV , μg/ gCre) was measured as intrarenal RAAS; urinary dopamine excretion rate ( U DAV , pg/ gCre) as intrarenal dopaminergic system; heart rate variabilities (HRV, calculated from 24‐h Holter‐ ECG) of non‐Gaussianity index λ 25s as sympathetic nerve activity; and power of high‐frequency ( HF) component or deceleration capacity ( DC) as parasympathetic nerve activity. At baseline, glomerular filtration rate correlated inversely with U AGTV ( r = −0.47, P = 0.04) and positively with U DAV ( r = 0.58, P = 0.009). HF was a determinant of night/day BP ratio ( β = −0.50, F = 5.8), rather than DC or λ 25s. During the acute phase of ARB treatment, a lower steady sodium balance was not achieved. Increase in daytime U N aV preceded restoration of BP rhythm, accompanied by decreased U AGTV ( r = −0.88, P = 0.05) and increased U DAV ( r = 0.87, P = 0.05), but with no changes in HRVs. Diminished sodium excretion can cause nondipper BP rhythm. This was attributable to intrarenal RAAS and dopaminergic system and impaired parasympathetic nerve activity. During the acute phase of ARB treatment, cooperative effects of ARB and intrarenal dopaminergic system exert natriuresis to restore circadian BP rhythm.