Effects of the novel nonsteroidal mineralocorticoid receptor blocker, esaxerenone (CS-3150),on blood pressure and urinary angiotensinogen in low-renin Dahl salt-sensitive hypertensive rats

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URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/28676
Title
Effects of the novel nonsteroidal mineralocorticoid receptor blocker, esaxerenone (CS-3150),on blood pressure and urinary angiotensinogen in low-renin Dahl salt-sensitive hypertensive rats
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Description

Abstract

Herein, we studied the effects of the novel nonsteroidal selective mineralocorticoid receptor (MR) blocker, esaxerenone, on blood pressure and renal injury in Dahl salt-sensitive (DSS) rats. We also monitored intact urinary and total angiotensinogen (AGT). DSS rats were given a normal salt diet (NS: 0.4% NaCl, n = 10), a high-salt diet (HS: 8% NaCl, n = 10), HS + esaxerenone (1 mg/kg/day, p.o., n = 10), or HS + losartan (angiotensin II receptor blocker, 10 mg/kg/day, p.o., n = 10) for 6 weeks. Glomerular and tubulointerstitial tissues were obtained via a laser capture method. HS-treated DSS rats developed hypertension, albuminuria, and glomerular injury, which were associated with increased glomerular desmin staining and reduced mRNA levels of glomerular podocin and nephrin. HS-treated DSS rats also showed tubulointerstitial fibrosis with an increase in renal oxidative stress (4-hydroxynonenal staining). The urinary ((total AGT-intact AGT)/intact AGT) ratio, an indicator of intrarenal renin activity, was significantly suppressed in HS-treated DSS rats. Treatment with esaxerenone significantly decreased blood pressure, while losartan did not. Furthermore, esaxerenone attenuated the development of albuminuria, glomerular injury, and tubulointerstitial fibrosis more than losartan did, and this effect was associated with reduced renal oxidative stress. These data indicate that esaxerenone has antihypertensive and renal protective effects in salt-dependent hypertensive mice with suppressed intrarenal renin activity, as indicated by low levels of the urinary (total AGT-intact AGT)/intact AGT ratio.

KEYWORDS:

Dahl salt-sensitive (DSS) rats; angiotensinogen (AGT); esaxerenone; intrarenal renin activity; nonsteroidal mineralocorticoid receptor (MR) blocker

(医博甲713)

Author
著者 李 磊
著者(ヨミ) リ レイ
著者(別表記) Li Lei
Publication Title
Hypertension Research
Publisher
Japanese Society of Hypertension
日本高血圧学会
Springer Nature
Publisher Aalternative
日本高血圧学会
Published Date
2018-12-26
ISSN
0916-9636
NCID
AA10847079
PMID
30587856
DOI
10.1038/s41440-018-0187-1
Resource Type
Thesis or Dissertation
Language
eng
Relation
出版社版DOIリンク(URL): https://doi.org/10.1038/s41440-018-0187-1
Resource URL
https://doi.org/10.1038/s41440-018-0187-1
Text Version
ETD
Grant ID
博甲第713号
Grant Date
2019-03-24
Degree Name
博士(医学)
Grantor
香川大学
Set
香川大学
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