Arginine administration increases circulating endothelial progenitor cells and attenuates tissue injury in a mouse model of hind limb ischemia/reperfusion

Abstract

Objective: This study investigated whether the administration of L-Arginine, the precursor of nitric oxide, increases the percentages of blood endothelial progenitor cells and protects against ischemia/reperfusion induced inflammatory response in a mouse model of hind-limb IR injury.

Method: C57BL/6 mice were randomized to one normal-control and four ischemia/reperfusion groups. The normal-control group did not undergo an ischemia/reperfusion procedure but mice in the ischemia/reperfusion groups were subjected to 150 min of unilateral hind-limb ischemia. The ischemia/reperfusion groups were subjected to either intravenous saline or L-Arginine (300 mg/kg body weight) administration before reperfusion and then sacrificed at either 24 h or 48 h after reperfusion. Blood and muscle tissues were collected for analysis.

Results: Ischemia/reperfusion injury led to a significant decrease in the percentage of blood endothelial progenitor cells and plasma nitric oxide concentration but plasma interleukin-6 levels and gene expression of inflammatory cytokines in injured muscle tissue were elevated. In contrast to the saline groups, those with L-Arginine administration were able to maintain a normal level of blood endothelial progenitor cells. In addition, after reperfusion, concentrations of nitric oxide, matrix metallopeptidase-9, and vascular endothelial growth factor in plasma were upregulated but keratinocyte-derived chemokine and monocyte chemoattractant protein-1 messenger RNA expressions in muscle were attenuated 48 h after reperfusion. Histologic findings also demonstrated a significant reduction of ischemia/reperfusion-induced muscle injury when L-Arginine was administered.

Conclusion: A single dose of L-Arginine administration before reperfusion increases the percentage of endothelial progenitor cells and reduces the inflammatory reaction locally and systemically after ischemia/reperfusion injury.

Keywords: Endothelial progenitor cell; Inflammation; Ischemia/reperfusion; L-Arginine; Nitric oxide; Vascular endothelial growth factor.