@article {52, title = {Vitamin D3, L-Arginine, L-Citrulline, and Antioxidant Supplementation Enhances Nitric Oxide Bioavailability and Reduces Oxidative Stress in the Vascular Endothelium {\textendash} Clinical Implications for Cardiovascular System}, journal = {Pharmacognosy Research}, volume = {12}, year = {2020}, month = {February 2020}, pages = {17-23}, type = {Original Article}, chapter = {17}, abstract = {

Background: Nitric oxide (NO) is a crucial signaling molecule which regulates the blood flow and prevents the adhesion of blood components to the vascular wall. A deficiency in bioavailable NO concentration is associated with the dysfunction of endothelial NO synthase (eNOS) and/or an increase in oxidative stress. The deficiency of bioavailable NO is a common denominator of several cardiovascular diseases, including diabetes, atherosclerosis, and hypertension. Materials and Methods: We used a nanomedical technology to elucidate the balance between bioavailable NO and oxidative stress (peroxynitrite ONOO-) in human umbilical vein endothelial cells (HUVECs) treated with a supplement containing L-arginine, L-citrulline, Vitamin D3, and antioxidants. Nanosensors, with a diameter of 200{\textendash}300 nm, are capable of measuring in situ NO and peroxynitrite (ONOO-) concentrations produced by single endothelial cells. Results: The ratio of the concentration of cytoprotective NO [NO] to the concentration of cytotoxic peroxynitrite [ONOO-] was used to estimate the efficiency of eNOS. HUVECs incubated with L-citrulline, L-arginine, and Vitamin D3 increased the [NO]/[ONOO-] ratio by 25\%, while in the presence of antioxidants, the increase was 15\%. The synergistic effect between the mix of L-arginine, L-citrulline, Vitamin D3, and antioxidants was a favorable increase of the overall [NO]/[ONOO-] ratio by 50\%. Conclusion: The findings of the study presented here clearly indicate that L-arginine, L-citrulline, and Vitamin D3 can significantly alter the function of the endothelium and NO production, in a favorable manner, while pointedly reducing ONOO- {\textendash} the main component of oxidative stress. This effect can be significantly potentiated in the presence of antioxidants.

}, keywords = {Antioxidant, Endothelium, L-arginine, L-citrulline, Nitric oxide, Peroxynitrite, Vitamin D3}, doi = {10.4103/pr.pr_79_19}, author = {Hazem Dawoud and Tadeusz Malinski} }