Pioglitazone prevents the endothelial dysfunction induced by ischemia and reperfusion in healthy subjects

J Cardiovasc Pharmacol. 2014 Oct;64(4):326-31. doi: 10.1097/FJC.0000000000000124.

Abstract

Background: No study has investigated whether pioglitazone (an agonist of peroxisome proliferator-activated receptor gamma) protects against ischemia and reperfusion (IR)-induced endothelial dysfunction in humans.

Methods and results: In the first crossover study, 20 volunteers were randomized to 1 week of pioglitazone (30 mg/d, postoperatively) or control (no treatment). In the second single-arm study, 15 volunteers received pioglitazone and the cyclooxygenase-2 inhibitor meloxicam for 1 week. On day 7, endothelium-dependent flow-mediated dilation (FMD) of the distal brachial artery was measured before and after IR (15 minutes of ischemia followed by 15 minutes of reperfusion in the proximal upper arm). Pre-IR brachial-artery diameter and FMD were similar across the 2 sessions (control, pioglitazone) in protocol 1 and between the 2 protocols. IR significantly blunted FMD after no treatment (pre-IR FMD: 10.2% ± 2.6%; post-IR FMD: 3.5% ± 1.9%, P < 0.01) but not after pioglitazone administration (pre-IR FMD: 9.7% ± 2.5%; post-IR FMD: 8.8% ± 2.9%, P = 0.11). This protective effect was accompanied by an increase in serum levels of the antioxidant enzyme extracellular superoxide dismutase and was not affected by concomitant administration of the cyclooxygenase-2 inhibitor meloxicam (P = 0.10).

Conclusions: In humans, pioglitazone provides potent protection against IR-induced endothelial dysfunction.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Blood Flow Velocity / drug effects
  • Brachial Artery / drug effects
  • Brachial Artery / physiopathology
  • Cross-Over Studies
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase 2 Inhibitors / pharmacokinetics
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / physiopathology*
  • Female
  • Healthy Volunteers
  • Humans
  • Male
  • Meloxicam
  • PPAR gamma / agonists
  • Pioglitazone
  • Reperfusion Injury / drug therapy
  • Reperfusion Injury / enzymology
  • Reperfusion Injury / physiopathology*
  • Superoxide Dismutase / blood
  • Thiazines / pharmacology
  • Thiazoles / pharmacology
  • Thiazolidinediones / administration & dosage
  • Thiazolidinediones / pharmacology*
  • Thiazolidinediones / therapeutic use
  • Vasodilation / drug effects*

Substances

  • Cyclooxygenase 2 Inhibitors
  • PPAR gamma
  • Thiazines
  • Thiazoles
  • Thiazolidinediones
  • Cyclooxygenase 2
  • Superoxide Dismutase
  • Meloxicam
  • Pioglitazone