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

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

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1
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.

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.

PMID:
24887686
DOI:
10.1097/FJC.0000000000000124
[Indexed for MEDLINE]
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