Allopurinol and valproic acid improve cardiac triglyceride and Na+-K+-ATPase activity independent of circulating aldosterone in female rats with glucose intolerance

Arch Physiol Biochem. 2022 Oct;128(5):1283-1289. doi: 10.1080/13813455.2020.1767148. Epub 2020 May 23.

Abstract

Context: Studies have shown that cardiac triglyceride accumulation and impaired Na+-K+-ATPase activity are linked to diabetes- related cardiovascular disease, particularly in women.Objectives: We hypothesised that allopurinol (ALL) and valproic acid (VPA) treatment would improve cardiac triglyceride and Na+-K+-ATPase activity independent of circulating aldosterone in Combined Oral Contraceptive (COC)-induced dysglycemiaMaterials and methods: Rats received COC (1.0 μg ethinylestradiol and 5.0 μg levonorgestrel; po) with or without ALL (1 mg; po) and VPA (20 mg; po) for 6 weeks.Results: COC-treatment led to impaired glucose tolerance, accumulated abdominal fat, dyslipidemia, elevated plasma MDA, PAI-1 and aldosterone levels and also reduced plasma nitric oxide bioavailability and cardiac Na+-K+-ATPase activity. However, either ALL or VPA treatment ameliorated these alterations comparably independent of elevated aldosterone levelDiscussion and conclusion: Our results suggest that either ALL or VPA would improve cardiac TG and Na+-K+-ATPase activity comparably in COC-treated rats, regardless of circulating aldosterone level.

Keywords: Cardiac Na+-K+-ATPase; cardiometabolic syndrome; hyperinsulinemia; hypeuricaemia; triglyceride.

MeSH terms

  • Adenosine Triphosphatases
  • Aldosterone
  • Allopurinol / pharmacology
  • Animals
  • Contraceptives, Oral, Combined
  • Female
  • Glucose Intolerance*
  • Humans
  • Insulin Resistance*
  • Levonorgestrel
  • Nitric Oxide
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Rats
  • Rats, Wistar
  • Sodium-Potassium-Exchanging ATPase
  • Triglycerides
  • Valproic Acid / pharmacology

Substances

  • Contraceptives, Oral, Combined
  • Plasminogen Activator Inhibitor 1
  • Triglycerides
  • Nitric Oxide
  • Aldosterone
  • Levonorgestrel
  • Valproic Acid
  • Allopurinol
  • Adenosine Triphosphatases
  • Sodium-Potassium-Exchanging ATPase