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J Physiol Volume 586, Number 14, 3525-3535, July 15, 2008 DOI: 10.1113/jphysiol.2008.151555
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CARDIOVASCULAR

Acute and chronic effects of vitamin C on endothelial fibrinolytic function in overweight and obese adult humans

Gary P. Van Guilder1, Greta L. Hoetzer1, Jared J. Greiner1, Brian L. Stauffer1,2,3 and Christopher A. DeSouza1,2

1 Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado, Boulder, CO, USA
2 Department of Medicine, University of Colorado at Denver, CO, USA
3 Denver Health Medical Center, Denver, CO, USA

We determined the effects of acute intra-arterial vitamin C administration and chronic oral vitamin C supplementation on the capacity of the endothelium to release t-PA in overweight and obese adults. Net endothelial t-PA release was determined in vivo in response to intrabrachial infusions of bradykinin and sodium nitroprusside in 33 sedentary adults: 10 normal-weight (BMI: 23.4 ± 0.5 kg m–2; 7M/3F); and 23 overweight/obese (BMI: 31.2 ± 0.8 kg m–2; 15M/8F). In 10 normal weight and eight overweight/obese adults the dose–response curves to bradykinin and sodium nitroprusside were repeated with a coinfusion of the antioxidant vitamin C (24 mg min–1). Seventeen of the 23 overweight/obese adults completed a 3 month chronic oral vitamin C (500 mg day–1) supplementation intervention. Intra-arterial administration of vitamin C significantly potentiated t-PA release in overweight/obese adults. Net release of t-PA was ~95% higher (P < 0.01) after (from –0.9 ± 1.1 to 94.6 ± 16.2 ng (100 ml tissue)–1 min–1) compared with before (from –0.8 ± 0.8 to 49.9 ± 7.7 ng (100 ml tissue)–1 min–1) vitamin C administration. Daily vitamin C supplementation significantly increased t-PA release in overweight/obese adults (from 0.2 ± 0.9 to 48.2 ± 6.5 ng (100 ml tissue)–1 min–1) before supplementation versus (0.3 ± 0.5 to 66.3 ± 8.7 ng (100 ml tissue)–1 min–1) after supplementation. These results indicate that the antioxidant vitamin C favourably affects the capacity of the endothelium to release t-PA in overweight/obese adults. Daily vitamin C supplementation represents an effective lifestyle intervention strategy for improving endothelial fibrinolytic regulation in this at-risk population.

(Received 24 January 2008; accepted after revision 19 May 2008; first published online 22 May 2008)
Corresponding author C. DeSouza: Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado, 354 UCB, Boulder, CO 80309, USA. Email: desouzac{at}colorado.edu







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