title: Pioglitazone prevents the endothelial dysfunction induced by ischemia and reperfusion in healthy subjects.
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.
  
  
  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.
authors.affiliation: Departments of *Cardiovascular Medicine; and †Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; and ‡Center of Ultrasonic Diagnostics, Okayama University Hospital, Okayama, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Sakatani
authors.forename: Toru
authors.initials: T
authors.lastname: Miyoshi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Oe
authors.forename: Yoko
authors.initials: Y
authors.lastname: Noda
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ohno
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Nakamura
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Saito
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Osawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Morita
authors.forename: Kunihisa
authors.initials: K
authors.lastname: Kohno
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
mesh_terms: D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects; D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology; D018592:Cross-Over Studies; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000493:pharmacokinetics; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D000077239:Meloxicam; D047495:PPAR gamma / Q000819:agonists; D000077205:Pioglitazone; D015427:Reperfusion Injury / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology*; D013482:Superoxide Dismutase / Q000097:blood; D013843:Thiazines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D047495:PPAR gamma; D013843:Thiazines; D013844:Thiazoles; D045162:Thiazolidinediones; D051546:Cyclooxygenase 2; D013482:Superoxide Dismutase; D000077239:Meloxicam; D000077205:Pioglitazone