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Azilsartan Causes Natriuresis Due to Its Sympatholytic Action in Kidney Disease

Azilsartan Causes Natriuresis Due to Its Sympatholytic Action in Kidney Disease

Satoshi Kidoguchi, Naoki Sugano, Koki Takane, Yasuhito Takahashi, Norihiko Morisawa, Miki Yarita, Naomi Hayashi-Ishikawa, Goro Tokudome, Takashi Yokoo

Hypertens Res. 2019 Oct;42(10):1507-1517.

PMID: 31138899

Abstract:

The sympathoinhibitory mechanism of azilsartan was investigated in an adenine-induced chronic renal failure model. Azilsartan exerted an antihypertensive effect, though BP elevation induced by adenine was marginal. The creatinine value was significantly lower in the azilsartan group (AZ) than in the vehicle group (VEH); furthermore, proteinuria was suppressed, and sodium excretion was augmented in the AZ group. The low frequency (LF) of systolic BP was suppressed (VEH: 4.07 ± 2.67 mmHg2 vs. AZ: 3.32 ± 1.93 mmHg2 P < 0.001), and the spontaneous baroreflex gain (sBRG) was augmented (VEH: 1.04 ± 0.62ms/mmHg vs. AZ: 1.38 ± 0.69 ms/mmHg, P < 0.001) in AZ. There were no significant differences in ACE1 and ACE2 expression between the groups, which indicated that the action of azilsartan on these components of the intrarenal renin-angiotensin-aldosterone system was comparatively small. Although NHE3, NKCC, and ENaC expression was similar between the groups, NaCl cotransporter (NCC) expression was markedly suppressed by azilsartan (P < 0.05). Thus, in a mild chronic kidney disease (CKD) model with slight BP elevation, the sympatholytic effect of ARB might be expected, and azilsartan might exert its natriuretic effect by NCC suppression achieved by sympathoinhibitory activity.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP147403030	Azilsartan		147403-03-0	Price

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