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L-arginine supplementation improves aortic vascular relaxation via NO-independent sGC/cGMP signaling in exercised rats


It is well established that physical training promotes beneficial effects on the vascular reactivity by improving the NO/cGMP signaling pathway [1]. L-Arginine (L-Arg) is a non-essential amino acid which plays a critical role in many organism functions such as pH regulation and endothelial cell membrane depolarization. Moreover, the benefits of the oral supplemention with L-Arg have been shown in hypercholesterolemic patients by inhibition of platelet aggregation and reduction of monocytes adhesion. In hypertensive rats, L-Arg supplemention reduces cardiac noradrenergic neurotransmission and enhanced angiogenesis in the hypoxic pulmonary hypertension. Although in human subjects the acute administration of L-Arg did not change hemodynamic and vascular responses to resistance exercise, no studies exist investigating the effect of chronic administration of L-Arg associated with dynamic exercise in the vascular responsiveness in rats. Thus, the aim of this work was to investigate the effect of L-Arg supplementation on the responsiveness of aortic rings in trained rats.


Male Wistar rats (344 ± 6 g) were divided into three groups: sedentary (SD), trained (TR) and trained supplemented (TRS). Animals were trained in a treadmill with an intensity of 70–80% of maximal oxygen consumption, in sessions of 60 minutes, 5 days a week. Run training (RT) was performed simultaneously to L-Arg intake (0.25 g/kg daily, given in the drinking water) for 4 weeks. Concentration-response curves were obtained for acetylcholine (ACh) and sodium nitroprusside (SNP) in isolated aortic rings. Plasma SOD and catalase concentrations were measured.


A lower body weight gain was found in TRS group (315 ± 9 g) as compared to SD (434 ± 10 g) and TR (392 ± 6 g) groups. Functional assays showed increase in the potency of the relaxing response to ACh in aortic rings in TR group (pEC50: 7.72 ± 0.03) and TRS group (pEC50: 7.53 ± 0.05), approximately 3.5 and 2.2-fold, respectively, as compared to SD (pEC50: 7.18 ± 0.06) without changes in the maximal responses (EMAX). The potency for SNP was markedly increased in TRS (pEC50: 9.21 ± 0.07) as compared to TR group (pEC50: 8.61 ± 0.10) and (pEC50: 7.90 ± 0.13). Plasma SOD activity was not changed in all groups (8.60 ± 4 U/ml, 7.75 ± 3 U/ml and 13 ± 2 U/ml, for SD, TR and TRS, respectively) whereas catalase level were reduced in TR and TRS groups (29 ± 6 μM and 19 ± 3 μM, respectively) as compared to SD group (44 ± 14 μM).


L-Arg supplementation associated with run training was effective to promote lower body weight gain. Furthermore, L-Arg supplementation associated with RT improved the relaxing response in aortic rings via NO-independent sGC/cGMP signaling.


  1. Zanesco A, Antunes E: Effects of exercise training on the cardiovascular system: pharmacological approaches. Pharmacol Ther. 2007, 114: 307-17. 10.1016/j.pharmthera.2007.03.010.

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The authors are grateful to Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP).

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Correspondence to Angelina Zanesco.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Zanesco, A., Priviero, F.M., Rojas-Moscoso, J.A. et al. L-arginine supplementation improves aortic vascular relaxation via NO-independent sGC/cGMP signaling in exercised rats. BMC Pharmacol 9 (Suppl 1), P78 (2009).

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