Transcriptomic profiling of SGLT2 inhibitor-treated hypertensive rats

Background: Sodium-glucose co-transporter-2 inhibitor (SGLT2i) compounds are antihyperglycemic medications that may improve cardiovascular disease (CVD) and chronic kidney disease prognosis in patients with diabetes mellitus. Methods: We conducted a detailed RNA-sequencing-based exploration of transcriptomic changes in response to empaglifozin in eight different tissuesfrom a rat model of spontaneous hypertension. Corresponding computational analyses were performed to analyze these data. Results: We discovered that empaglifozin exerts potent transcriptomic effects upon various tissues. Empaglifozin therapy may exert effects upon the kidney by impacting aldosterone-regulated sodium resorption, lyosome. The functional enrichment of DEGs indicated empaglifozin may regulate blood pressure, blood glucose, lipid homeostasis and nervous system in SHR. Consistent with our RNA-Seq findings, following 1-month empaglifozin administration, immunofluorescence staining revealed enhanced renal expression of caveolin-1. Conclusions: These findings offer value as a foundation guiding further exploration regarding the effects associated with SGLT2i therapy in the context of hypertension. spontaneous hypertension rat (male, aged 8 weeks, 220-260g) were treated with empaglifozin by gavage at the dose of 10 mg/kg/d (n=3) or saline vehicle control(n=3) daily for a period of 30 days. Then RNA-sequencing-based exploration of transcriptomic changes in response to empaglifozin in eight different tissues (i.e., atrial, aortic, ventricular, white adipose, brown adipose, renal, lung, and brain) were performed.