Sodium-glucose co-transporter 2 inhibition does not improve the acute pressure natriuresis response in rats with Type 1 diabetes

Natalie Jones, Hannah Costello, Marie-Louise Monaghan, Kevin Stewart, David Binnie, Joanne Marks, Matthew A Bailey, Geoff Culshaw

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Type 1 diabetes mellitus (T1DM) leads to serious complications including premature cardiovascular and kidney disease. Hypertension contributes importantly to these adverse outcomes. The renal pressure natriuresis (PN) response, a key regulator of blood pressure (BP), is impaired in rats with T1DM as tubular sodium reabsorption fails to down-regulate with increasing BP. We hypothesized that sodium-glucose co-transporter 2 (SGLT2) inhibitors, which reduce cardiovascular risk in kidney disease, would augment the PN response in T1DM rats. Non-diabetic or T1DM (35-50 mg/kg streptozotocin IP) adult male Sprague-Dawley rats were anesthetized (thiopental 50mg/kg IP) and randomized to receive either dapagliflozin (10 mg/kg IV) or vehicle. Baseline sodium excretion was measured and then BP was increased by sequential arterial ligations to induce the PN response. In non-diabetic animals, the natriuretic and diuretic response to increasing BP was not augmented by dapagliflozin. Dapagliflozin induced glycosuria but this was not influenced by BP. In T1DM rats the PN response was impaired. Dapagliflozin again increased urinary glucose excretion but did not enhance PN. Inhibition of SGLT2 does not enhance the PN response in rats, either with or without T1DM. SGLT2 makes only a minor contribution to tubular sodium reabsorption and does not contribute to the impaired PN response in T1DM.
Original languageEnglish
Pages (from-to)480-490
Number of pages10
JournalExperimental Psychology
Issue number3
Early online date15 Jan 2023
Publication statusE-pub ahead of print - 15 Jan 2023

Keywords / Materials (for Non-textual outputs)

  • blood pressure
  • diabetes
  • pressure natriuresis
  • SLGT2
  • sodium balance


Dive into the research topics of 'Sodium-glucose co-transporter 2 inhibition does not improve the acute pressure natriuresis response in rats with Type 1 diabetes'. Together they form a unique fingerprint.

Cite this