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

Yuka Sakatani, Toru Miyoshi, Hiroki Oe, Yoko Noda, Yuko Ohno, Kazufumi Nakamura, Yukihiro Saito, Kazuhiro Osawa, Hiroshi Morita, Kunihisa Kohno, Hiroshi Ito

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


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 flowmediated 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% 6 2.6%; post-IR FMD: 3.5% 6 1.9%, P , 0.01) but not after pioglitazone administration (pre-IR FMD: 9.7% 6 2.5%; post- IR FMD: 8.8% 6 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.

Original languageEnglish
Pages (from-to)326-331
Number of pages6
JournalJournal of cardiovascular pharmacology
Issue number4
Publication statusPublished - Oct 1 2014


  • Brachial artery
  • Cyclooxygenase-2 pathway
  • Endothelium
  • Flow-mediated dilation
  • Ischemia and reperfusion
  • Pioglitazone

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine


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