Effects of diuretics on sodium-dependent glucose cotransporter 2 inhibitor-induced changes in blood pressure in obese rats suffering from the metabolic syndrome. Issue 5 (May 2016)

• Record Type: Journal Article
• Authors: Rahman, Asadur; Kittikulsuth, Wararat; Fujisawa, Yoshihide; Sufiun, Abu; Rafiq, Kazi; Hitomi, Hirofumi; Nakano, Daisuke; Sohara, Eisei; Uchida, Shinichi; Nishiyama, Akira
• Is Part Of: Journal of hypertension. Volume 34:Issue 5(2016:May)
• Publication Date: 2016-05
• Subjects: diuretics -- glucose homeostasis -- hypertension -- insulin resistance -- metabolic syndrome -- sodium-dependent glucose cotransporter 2 inhibitor; Hypertension -- Periodicals; Hypertension -- Periodicals; 616.132005
• DOI: 10.1097/HJH.0000000000000871
• Languages: English
• ISSNs: 1473-5598

Abstract

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. Abstract : Supplemental Digital Content is available in the text