Empagliflozin modulates renal sympathetic and heart rate baroreflexes in a rabbit model of diabetes Academic Article uri icon

abstract

  • AIMS/HYPOTHESIS:We determined whether empagliflozin altered renal sympathetic nerve activity (RSNA) and baroreflexes in a diabetes model in conscious rabbits. METHODS:Diabetes was induced by alloxan, and RSNA, mean arterial pressure (MAP) and heart rate were measured before and after 1 week of treatment with empagliflozin, insulin, the diuretic acetazolamide or the ACE inhibitor perindopril, or no treatment, in conscious rabbits. RESULTS:Four weeks after alloxan administration, blood glucose was threefold and MAP 9% higher than non-diabetic controls (p < 0.05). One week of treatment with empagliflozin produced a stable fall in blood glucose (-43%) and increased water intake (+49%) but did not change RSNA, MAP or heart rate compared with untreated diabetic rabbits. The maximum RSNA to hypotension was augmented by 75% (p < 0.01) in diabetic rabbits but the heart rate baroreflex was unaltered. Empagliflozin and acetazolamide reduced the augmentation of the RSNA baroreflex (p < 0.05) to be similar to the non-diabetic group. Noradrenaline (norepinephrine) spillover was similar in untreated diabetic and non-diabetic rabbits but twofold greater in empagliflozin- and acetazolamide-treated rabbits (p < 0.05). CONCLUSIONS/INTERPRETATION:As empagliflozin can restore diabetes-induced augmented sympathetic reflexes, this may be beneficial in diabetic patients. A similar action of the diuretic acetazolamide suggests that the mechanism may involve increased sodium and water excretion. Graphical abstract.

authors

  • Gueguen, C
  • Burke, SL
  • Barzel, B
  • Eikelis, N
  • Watson, Anna MD
  • Jha, JC
  • Jackson, KL
  • Sata, Y
  • Lim, Kyungjoon
  • Lambert, GW
  • Jandeleit-Dahm, KAM
  • Cooper, ME
  • Thomas, MC
  • Head, GA

publication date

  • 2020