PS 13-28 EFFECTS OF A SGLT2 INHIBITOR ON RENAL EXPRESSION OF SODIUM TRANSPORTERS IN OBESE METABOLIC SYNDROME RATS. (September 2016)

• Record Type: Journal Article
• Authors: Rahman, Asadur; Kittikulsuth, Wararat; Hitomi, Hirofumi; Nakano, Daisuke; Nishiyama, Akira
• Is Part Of: Journal of hypertension. Volume 34:(2016) Supplement 1
• Publication Date: 2016-09
• Subjects: Hypertension -- Periodicals; Hypertension -- Periodicals; 616.132005
• DOI: 10.1097/01.hjh.0000501121.42524.74
• Languages: English
• ISSNs: 1473-5598

Abstract

Abstract : Objective: Experiments were carried out to examine the effects of a sodium-glucose co-transporter 2 (SGLT2) inhibitor on renal expression of glucose and sodium transporters in metabolic syndrome SHR/NDmcr-cp (+/+) (SHRcp) rats. Design and Method: Male 13-week-old SHRcp rats were treated with vehicle or a SGLT2 inhibitor, luseogliflozin (10 mg/kg) daily by oral gavage for 7 weeks. Immunohistochemistry and/or Western blotting were performed to investigate the changes in renal protein levels of glucose and sodium transporters. Results: Treatment with luseogliflozin did not change creatine clearance. Urinary excretion rates of glucose and electrolytes (Na +, K +, Cl - ) were significantly increased after 5 weeks of treatment in luseogliflozin-treated SHRcp, whereas urine osmolality was significantly decreased. Luseogliflozin significantly decreased SGLT2 expression and increased protein levels of sodium-hydrogen exchanger 3 (NHE3) and phosphorylated sodium chloride co-transporter (p-NCC). On the other hand, no significant change was observed in epithelial sodium channel (ENaC) subunits and aquaporin 2 (AQP2) proteins levels following luseogliflozin treatment. Conclusions: These data suggest that SGLT2 inhibitor-induced diuresis is not predominantly induced by changes in expression of sodium transporters. Compensatory increases in renal NHE3 and p-NCC levels may be accompanied by SGLT2 inhibitor-induced increases in sodium and water load in proximal and distal tubules, respectively.