Effects of diuretics on SGLT2 inhibitor-induced changes in blood pressure in obese rats suffering from the metabolic syndrome

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URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/28761
Title
Effects of diuretics on SGLT2 inhibitor-induced changes in blood pressure in obese rats suffering from the metabolic syndrome
File
Description

Abstract
OBJECTIVE:

Experiments were carried out to investigate whether diuretics (hydrochlorothiazide + furosemide) impact on the effects of a sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor on glucose metabolism and blood pressure (BP) in metabolic syndrome SHR/NDmcr-cp(+/+) rats (SHRcp).
METHODS:

Male 13-week-old SHRcp were treated with: vehicle; the SGLT2-inhibitor luseogliflozin (10 mg/kg per day); diuretics (hydrochlorothiazide; 10 mg/kg/day + furosemide; 5 mg/kg per day); or luseogliflozin + diuretics (n = 5-8 for each group) daily by oral gavage for 5 weeks. BP and glucose metabolism were evaluated by a telemetry system and oral glucose tolerance test, respectively.
RESULTS:

Vehicle-treated SHRcp developed nondipper type hypertension (dark vs. light-period mean arterial pressure: 148.6 ± 0.7 and 148.0 ± 0.7 mmHg, respectively, P = 0.2) and insulin resistance. Compared with vehicle-treated animals, luseogliflozin-treated rats showed an approximately 4000-fold increase in urinary excretion of glucose and improved glucose metabolism. Luseogliflozin also significantly decreased BP and turned the circadian rhythm of BP from a nondipper to dipper pattern (dark vs. light-period mean arterial pressure: 138.0 ± 1.6 and 132.0 ± 1.3 mmHg, respectively, P < 0.01), which were associated with a significant increase in urinary excretion of sodium. Addition of diuretics did not influence luseogliflozin-induced improvement of glucose metabolism and circadian rhythm of BP in SHRcp.
CONCLUSION:

These data suggest that a SGLT2 inhibitor elicits its beneficial effects on glucose metabolism and hypertension in study participants with metabolic syndrome undergoing treatment with diuretics.

Keywords:

diuretics; glucose homeostasis; hypertension; insulin resistance; metabolic syndrome; sodium-dependent glucose cotransporter 2 inhibitor

(医博乙277)

Author
著者 MD. ASADUR RAHMAN
著者(ヨミ) エムディ アサドウール ラフマン
著者(別表記) Rahman Asadur
Publication Title
Journal of Hypertension
Publication Title Alternative
J Hypertens.
Volume
34
Issue
5
Start Page
893
End Page
906
Publisher
International Society of Hypertension
Wolters Kluwer Health
Published Date
2016-05
ISSN
0263-6352
NCID
AA10644107
PMID
26982381
DOI
10.1097/HJH.0000000000000871
Resource Type
Thesis or Dissertation
Language
eng
Resource URL
https://doi.org/10.1097/HJH.0000000000000871
Rights
Copyright © 2016 Wolters Kluwer Health, Inc.
"This is the Accepted Version of the following article: Effects of diuretics on sodium-dependent glucose cotransporter 2 inhibitor-induced changes in blood pressure in obese rats suffering from the metabolic syndrome; Journal of Hypertension; Volume 34 - Issue 5 (2016) Pages: 893-906; doi: 10.1097/HJH.0000000000000871, which has been published in final form at https://doi.org/10.1097/HJH.0000000000000871 . "
Text Version
ETD
Grant ID
博乙第277号
Grant Date
2016-03-04
Degree Name
博士(医学)
Grantor
香川大学
Set
香川大学
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