title: A sodium-glucose co-transporter 2 inhibitor empagliflozin prevents abnormality of circadian rhythm of blood pressure in salt-treated obese rats.
abstract: Studies were performed to examine the effects of the selective sodium-glucose co-transporter 2 (SGLT2) inhibitor empagliflozin on urinary sodium excretion and circadian blood pressure in salt-treated obese Otsuka Long Evans Tokushima Fatty (OLETF) rats. Fifteen-week-old obese OLETF rats were treated with 1% NaCl (in drinking water), and vehicle (0.5% carboxymethylcellulose, n=10) or empagliflozin (10 mg kg(-1)per day, p.o., n=11) for 5 weeks. Blood pressure was continuously measured by telemetry system. Glucose metabolism and urinary sodium excretion were evaluated by oral glucose tolerance test and high salt challenge test, respectively. Vehicle-treated OLETF rats developed non-dipper type blood pressure elevation with glucose intolerance and insulin resistance. Compared with vehicle-treated animals, empagliflozin-treated OLETF rats showed an approximately 1000-fold increase in urinary glucose excretion and improved glucose metabolism and insulin resistance. Furthermore, empagliflozin prevented the development of blood pressure elevation with normalization of its circadian rhythm to a dipper profile, which was associated with increased urinary sodium excretion. These data suggest that empagliflozin elicits beneficial effects on both glucose homeostasis and hypertension in salt-replete obese states.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan.|Division of Nephrology, Department of Medicine, Showa University School of Medicine, Yokohama, Japan.
authors.forename: Yui
authors.initials: Y
authors.lastname: Takeshige
authors.affiliation: Life Science Research Center, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Fujisawa
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Asadur
authors.initials: A
authors.lastname: Rahman
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Wararat
authors.initials: W
authors.lastname: Kittikulsuth
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nakano
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Mori
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Masaki
authors.affiliation: Department of Cardiology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ohmori
authors.affiliation: Department of Cardiology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kohno
authors.affiliation: Division of Nephrology, Department of Medicine, Showa University School of Medicine, Yokohama, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ogata
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D001786:Blood Glucose; D001794:Blood Pressure / Q000187:drug effects*; D002940:Circadian Rhythm / Q000187:drug effects*; D005951:Glucose Tolerance Test; D005960:Glucosides / Q000494:pharmacology* / Q000627:therapeutic use; D006706:Homeostasis / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007333:Insulin Resistance; D009765:Obesity / Q000503:physiopathology*; D051381:Rats; D020334:Rats, Inbred OLETF; D017673:Sodium Chloride, Dietary / Q000494:pharmacology; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005960:Glucosides; D007004:Hypoglycemic Agents; C490299:Slc5a2 protein, mouse; D017673:Sodium Chloride, Dietary; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C570240:empagliflozin
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