Aldosterone Induces Vasoconstriction in Individuals with Type 2 Diabetes: Effect of Acute Antioxidant Administration

J Clin Endocrinol Metab. 2021 Mar 8;106(3):e1262-e1270. doi: 10.1210/clinem/dgaa867.

Abstract

Context: Individuals with type 2 diabetes have an increased risk of endothelial dysfunction and cardiovascular disease. Plasma aldosterone could contribute by reactive oxygen species-dependent mechanisms by inducing a shift in the balance between a vasoconstrictor and vasodilator response to aldosterone.

Objective: We aimed to investigate the acute vascular effects of aldosterone in individuals with type 2 diabetes compared with healthy controls and if infusion of an antioxidant (n-acetylcysteine [NAC]) would alter the vascular response.

Methods: In a case-control design, 12 participants with type 2 diabetes and 14 healthy controls, recruited from the general community, were studied. Leg hemodynamics were measured before and during aldosterone infusion (0.2 and 5 ng min-1 [L leg volume]-1) for 10 minutes into the femoral artery with and without coinfusion of NAC (125 mg kg-1 hour-1 followed by 25 mg kg-1 hour-1). Leg blood flow and arterial blood pressure was measured, and femoral arterial and venous blood samples were collected.

Results: Compared with the control group, leg blood flow and vascular conductance decreased during infusion of aldosterone at the high dose in individuals with type 2 diabetes, whereas coinfusion of NAC attenuated this response. Plasma aldosterone increased in both groups during aldosterone infusion and there was no difference between groups at baseline or during the infusions.

Conclusion: These results suggests that type 2 diabetes is associated with a vasoconstrictor response to physiological levels of infused aldosterone and that the antioxidant NAC diminishes this response.

Trial registration: ClinicalTrials.gov NCT03017703.

Keywords: aldosterone; blood flow; human; n-acetylcysteine; type 2 diabetes; vasoconstriction.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / administration & dosage
  • Acetylcysteine / pharmacology*
  • Adult
  • Aldosterone / administration & dosage
  • Aldosterone / blood
  • Aldosterone / pharmacology*
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacology
  • Case-Control Studies
  • Denmark
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Female
  • Femoral Artery / drug effects
  • Femoral Artery / physiopathology
  • Hemodynamics / drug effects
  • Humans
  • Leg / blood supply
  • Male
  • Middle Aged
  • Regional Blood Flow / drug effects
  • Vasoconstriction / drug effects*

Substances

  • Antioxidants
  • Aldosterone
  • Acetylcysteine

Associated data

  • ClinicalTrials.gov/NCT03017703