OS 32-05 EFFECTS OF SGLT2 INHIBITORS ON CIRCADIAN RHYTHM OF BLOOD PRESSURE IN RATS

Abstract

Disrupted circadian rhythm of blood pressure is associated with cardiovascular events in metabolic syndrome and obesity. Experiments were conducted to examine the effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on circadian rhythm of blood pressure in a genetic model of obese metabolic syndrome (SHR/NDmcr-cp (+/+) (SHRcp)) and salt-treated obese Otsuka Long Evans Tokushima Fatty (OLETF) rats. Luseogliflozin (10 mg/kg/day, p.o.) and empagliflozin (10 mg/kg/day, p.o.) were administered for 5 weeks in metabolic syndrome SHRcp rats and 1% NaCl (in drinking water)-treated obese OLETF rats, respectively. Blood pressure was measured continuously by telemetry system. Glucose metabolism and insulin resistance were evaluated by oral glucose tolerance test. Both SHRcp and salt-treated OLETF rats developed non-dipper type of hypertension with altered glucose metabolism and insulin resistance. Administration of luseogliflozin and empagliflozin resulted in a remarkable increase in urinary glucose excretion and improved glucose metabolism and insulin resistance in SHRcp and salt-treated OLETF rats, respectively. Furthermore, luseogliflozin and empagliflozin significantly attenuated the development of hypertension with normalization of circadian rhythm of blood pressure, which was associated with an increase in urinary sodium excretion. These data suggest that SGLT2 inhibitors elicit beneficial effects on circadian rhythm of blood pressure during the development of hypertension in subjects with metabolic syndrome and obese.