Effect of a SGLT2 inhibitor on the systemic and intrarenal renin-angiotensin system in subtotally nephrectomized rats

J Pharmacol Sci. 2018 Jun;137(2):220-223. doi: 10.1016/j.jphs.2017.10.006. Epub 2017 Oct 28.

Abstract

We aimed to examine the effects of a sodium glucose co-transporter 2 (SGLT2) inhibitor on systemic and intrarenal renin-angiotensin system (RAS) in subtotally nephrectomized non-diabetic rats, a model of chronic kidney disease (CKD). Oral administration of the selective SGLT2 inhibitor, TA-1887 (10 mg/kg/day), for 10 weeks induced glycosuria. However, plasma renin activity, plasma angiotensinogen levels, kidney angiotensin II contents and renal injury were not significantly affected by TA-1887. These data indicate that chronic treatment with an SGLT2 inhibitor does not activate the systemic and intrarenal RAS in subjects with non-diabetic CKD.

Keywords: Chronic kidney disease (CKD); Renin–angiotensin system (RAS); SGLT2 inhibitor.

MeSH terms

  • Administration, Oral
  • Angiotensin II / metabolism
  • Angiotensinogen / blood
  • Animals
  • Disease Models, Animal
  • Glucosides / therapeutic use*
  • Glycosuria / chemically induced
  • Indoles / therapeutic use*
  • Kidney / metabolism*
  • Male
  • Nephrectomy
  • Rats, Sprague-Dawley
  • Renal Insufficiency, Chronic / metabolism*
  • Renin / blood
  • Renin-Angiotensin System / drug effects*
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors*

Substances

  • Glucosides
  • Indoles
  • Slc5a2 protein, rat
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors
  • Angiotensinogen
  • Angiotensin II
  • Renin