Effects of an SGLT2 inhibitor on the salt sensitivity of blood pressure and sympathetic nerve activity in a nondiabetic rat model of chronic kidney disease

Abstract

The glucose-lowering effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors is reduced in patients with diabetes who have chronic kidney disease (CKD). In the present study, we examined the effect of an SGLT2 inhibitor on the salt sensitivity of blood pressure (BP), circadian rhythm of BP, and sympathetic nerve activity (SNA) in nondiabetic CKD rats. Uninephrectomized Wistar rats were treated with adenine (200 mg/kg/day) for 14 days. After stabilization with a normal-salt diet (NSD, 0.3% NaCl), a high-salt diet (HSD, 8% NaCl) was administered. Mean arterial pressure (MAP) was continuously monitored using a telemetry system. We also analyzed the low frequency (LF) of systolic arterial pressure (SAP), which reflects SNA. In adenine-induced CKD rats, HSD consumption for 5 days significantly increased the mean MAP from 106 ± 2 to 148 ± 3 mmHg. However, MAP was decreased to 96 ± 3 mmHg within 24 h after switching back to a NSD (n = 7). Treatment with an SGLT2 inhibitor, luseogliflozin (10 mg/kg/day, p.o., n = 7), significantly attenuated the HSD-induced elevation of MAP, which was associated with a reduction in LF of SAP. These data suggest that treatment with an SGLT2 inhibitor attenuates the salt sensitivity of BP, which is associated with SNA inhibition in nondiabetic CKD rats.

Keywords: Blood pressure; Chronic kidney disease; Rat; Salt; Sodium-glucose cotransporter 2 inhibitor; Sympathetic nerve activity.