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

• Published in: Journal of cardiovascular pharmacology Vol. 64; no. 4; p. 326
• Main Authors: Sakatani, Yuka, Miyoshi, Toru, Oe, Hiroki, Noda, Yoko, Ohno, Yuko, Nakamura, Kazufumi, Saito, Yukihiro, Osawa, Kazuhiro, Morita, Hiroshi, Kohno, Kunihisa, Ito, Hiroshi
• Format: Journal Article
• Language: English
• Published: United States 01.10.2014
• Subjects: 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; PPAR gamma - agonists; 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
• ISSN: 1533-4023
• DOI: 10.1097/FJC.0000000000000124

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