1109-P: Blood Pressure (BP) Lowering Effect of Empagliflozin Is Related to Decreased L-Arginine Clearance in Diabetic Rats - Archive ouverte HAL Access content directly
Journal Articles Diabetes Year : 2020

1109-P: Blood Pressure (BP) Lowering Effect of Empagliflozin Is Related to Decreased L-Arginine Clearance in Diabetic Rats

Daniel Veyel
  • Function : Author
Bartlomiej Krawczyk
  • Function : Author
Michael Pieper
  • Function : Author
Michael Mark
  • Function : Author
Eric Mayoux
  • Function : Author

Abstract

Introduction: The availability of L-arginine is the rate-limiting factor in Nitric Oxide (NO) synthesis, a potent vasodilatory factor. L-arginine plasma levels are blunted in diabetes, thus L-arginine supplementation decreases BP in animal diabetic models, and type 2 diabetic patients. Renal reabsorption of filtered L-arginine in the proximal tubule is mainly sodium dependent. Higher filtered glucose load in diabetes may alter sodium gradient via higher glucose reabsorption by sodium-glucose cotransporters (SGLTs). Purpose: The mechanism by which SGLT2 inhibitors, such as Empagliflozin, decrease BP in type 2 diabetic patients, is still unknown. We hypothesize that SGLT2 inhibitors could decrease the urinary excretion of L-arginine, by restoring sodium gradient necessary for L-arginine reabsorption in the proximal tubule. Methods: Male obese Zucker diabetic fatty/Spontaneously hypertensive heart failure hybrid (ZSF1) rats and their lean littermates (CTR) received either Empagliflozin or vehicle for 6 weeks. Levels of L-arginine in urine and plasma were quantified via Liquid Chromatography-Mass Spectrometry. Plasmatic cGMP level, a marker of NO production and urinary 8-hydroxydeoxyguanosine (8-OHdG) level, a marker of oxidative stress, were measured. Results: The urinary level of L-arginine was higher in ZSF-1 rats compared to CTR ones, and plasmatic concentrations of L-arginine were lower in ZSF-1 rats compared to CTR ones. Both parameters were significantly reversed by Empagliflozin. Empagliflozin treatment increased plasmatic cGMP and decreased urinary 8-OHdG in diabetic rats. Conclusion: Empagliflozin decreased urinary excretion of L-arginine, associated with an increased plasmatic concentration of L-arginine and cGMP, and decreased oxidative stress in diabetic rats. This suggests that Empagliflozin increased NO production and bioavailability. Such effects might contribute to the BP lowering effect of Empagliflozin in diabetics. Disclosure S. Khemais-Benkhiat: Employee; Self; Boehringer Ingelheim International GmbH. D. Veyel: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. V. Schini-Kerth: Research Support; Self; Boehringer Ingelheim International GmbH. B. Krawczyk: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. M. Pieper: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. M. Mark: Employee; Self; Boehringer Ingelheim International GmbH. E. Mayoux: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc.

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Hematology
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Dates and versions

hal-03899695 , version 1 (15-12-2022)

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Sonia Khemais-Benkhiat, Daniel Veyel, Valerie Schini-Kerth, Bartlomiej Krawczyk, Michael Pieper, et al.. 1109-P: Blood Pressure (BP) Lowering Effect of Empagliflozin Is Related to Decreased L-Arginine Clearance in Diabetic Rats. Diabetes, 2020, 69 (Supplement_1), ⟨10.2337/db20-1109-P⟩. ⟨hal-03899695⟩

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