Abstract
Congestive heart failure (CHF) is a pathophysiological state characterized by the activation of neurohumoral systems and sodium and water retention. Previously we have shown enhanced tonic renal sympathetic nerve activation in CHF increases the expression and functional activity of renal sodium-glucose co-transporter 2 (SGLT2). This study was to investigate the beneficial effects of chronic SGLT2 inhibition on renal sympathetic activity in CHF. Three weeks after coronary ligation surgery to induce CHF, Sprague Dawley rats were treated with SGLT2 inhibitor dapagliflozin (1mg/kg/day) via subcutaneous infusion for two weeks. Cardiac function, hemodynamic parameters, renal sympathetic nerve activity (both efferent and afferent activity), and renal excretory function were monitored. Compared with saline infusion, dapagliflozin significantly attenuated left ventricular end-diastolic pressure (13.6 ± 3.7 vs. 20.3 ± 3.9 mmHg, P<0.05) in rats with CHF. A slight decrease in mean arterial pressure was observed by telemetry in dapagliflozin-treated CHF rats. Dapagliflozin infusion increased urine volume (18.6 ± 3.1 vs. 9.2 ± 3.8 ml/day, P<0.05) and sodium excretion (4.8 ± 1.0 vs. 2.0 ± 0.6 mEq/day, P<0.05) in CHF rats. In CHF rats, dapagliflozin reduced urinary norepinephrine excretion (4.6 ± 0.4 vs. 8.3 ± 0.7 ug/day, P<0.05), basal renal sympathetic nerve activity (2.1 ± 0.3 vs. 3.8 ± 0.4 uV.s, P<0.05), and renal afferent sympathetic nerve activity (35.6 ± 5.7 vs. 58.4 ± 5.8 %Amax, P<0.05). These data suggest that chronic long-term treatment with SGLT2 inhibition exerts a potential protective effect on CHF through attenuating renal afferent and efferent sympathetic activity and consequent reduction in sodium retention. Funded by NIH R01-DK-114663 & R01-DK-129311 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
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