The Effects of Low-dose Empagliflozin on Cardiac Function in a Rat Model of Streptozotocin-induced Diabetes
Abstract
Purpose: Diabetes mellitus is a metabolic disorder leading to cardiovascular complications. Both in vivo cardiac function and β-adrenoceptor (β-AR) mediated responsiveness have been demonstrated to be blunted in the diabetic heart. Sodium glucose co-transporter-2 (SGLT2) inhibitors, such as empagliflozin (EMPA) have shown cardioprotective effects in patients and in some animal models. In this study, we aimed to investigate the effects of low-dose EMPA (10 mg/kg/day) on in vivo cardiac function and β-AR-mediated contractile response in streptozotocin (STZ)-induced diabetic rats. Methods: 11-12 week old male Sprague Dawley rats were divided into 4 groups; control, EMPA-treated control, diabetic, EMPA-treated diabetic. Diabetes was induced by STZ injection (40 mg/kg, i.p.). After 13-16 weeks, some of the diabetic and control rats were treated with a low dose of EMPA (10 mg/kg/day, oral gavage, once a day) or vehicle for another 8 weeks. At study end, in vivo cardiac function was evaluated by pressure-volume loop analysis. β-AR mediated contractile response was determined using isoprenaline in papillary muscle preparations. Results: EMPA did not change cardiac function in control rats. Diabetic rats had a reduced heart rate, cardiac output, stroke work, +dp/dt and -dp/dt and increased isovolumic relaxation, whereas in vitro responses were reduced to a minor extent. Treatment with EMPA showed a trend for improvement of some but not all parameters. Conclusion: Our results indicate…
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