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Eur J Cardiothorac Surg 2003;23:626-632
© 2003 Elsevier Science NL

Age-related changes in the protective effect of chronic administration of L-arginine on post-ischemic recovery of endothelial function

Koki Nakamuraa, Sharif Al-Ruzzeha, Adrian H. Chestera, Ann Dewarb, Steve Rotheryc, Nicholas J. Seversc, Magdi H. Yacouba, Mohamed Amrania*

a National Heart and Lung Institute, Heart Science Centre, Harefield Hospital, Harefield, Middlesex UB9 6JH, UK
b Electron Microscopy Unit, Brompton Hospital, London, UK
c Cell Biology Department, Brompton Hospital, London, UK

Received 6 August 2002; received in revised form 23 December 2002; accepted 7 January 2003.

* Corresponding author. Tel.: +44-1895-828550; fax: +44-1895-828992
e-mail: mr.amrani{at}rbh.nthames.nhs.uk

Objective: The aim of this study was to assess the effect of chronic administration of L-arginine (LA) on vascular functions as well as its age-related changes. Methods: Male Sprague–Dawley rats aged 1, 4, 8 and 16 months were divided into control and LA groups, which were administered LA (4 mg/ml) for 6 weeks. Isolated heart perfusion was performed, followed by cardioplegic arrest for 4 h at 4°C and reperfusion. Vascular functions were assessed through observations of pre-/post-ischemic coronary flow response to 5-hydroxytryptamine (5-HT) and glyceryl trinitrate (GTN). Ultrastructure was studied after the same ischemia-reperfusion. Results: A significant improvement of percentage recovery (post-/pre-ischemic value) of response to 5-HT were seen in 4 and 8 months LA group when compared to the control (84.2±14.0 vs. 33.9±12.5 (P<0.05) and 97.0±23.2 vs. 21.5±9.7 (P<0.05), respectively). Furthermore, 8 months LA group had better percentage recovery of response to GTN (124.5±41.6 vs. 47.7±6.3, P<0.05). Ultrastructural study showed no significant differences between the groups in any age. Conclusions: Chronic oral administration of LA enhanced the post-ischemic recovery of vascular function in the young adult and adult hearts, but not in the infant and elderly.

Key Words: Aging • Endothelial function • Ischemia • Nitric oxide • Reperfusion






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