Systemic arterial hypertension is the major cause of morbidity and mortality worldwide, and if not managed properly, it could lead to the development of cardiovascular diseases (CVDs). Hypertension is characterized by persistent high blood pressure. It is generally managed with medications (ACE inhibitors, calcium channel blockers, diuretics and angiotensin II receptor blockers) and lifestyle changes (reduced sodium intake, increased potassium intake, weight loss, and increased physical activity)1. Besides this, there are reports that L-arginine could lower blood pressure. In this article, we will focus on the science behind the hypotensive role of L-arginine.
L-arginine ((S)-2-Amino-5-guanidinopentanoic acid) is one of the 20 genetically encoded amino acids found in proteins. L-arginine is the precursor of nitric oxide (NO), an important signalling molecule in humans. Nitric oxide synthases are the enzymes responsible for the oxidation of L-arginine to nitric oxide and L-citrulline2. Nitric oxide produced by endothelial cells of the blood vessels is reported to act as a vasodilator and regulate vascular function.
Fig. 1 Structure of L-arginine
(Adapted from https://pubchem.ncbi.nlm.nih.gov/)
NO diffuses into the smooth muscle cells of blood vessels and activates guanylyl cyclase, which converts GTP into a secondary messenger (cGMP). Cyclic GMP leads to reduced intracellular calcium levels and vasodilation3. Various reports suggest that NO deficiency is associated with hypertension. Additionally, impaired nitric oxide production by endothelial cells can lead to the onset and progression of CVDs (Fig. 2)4.
Fig.2 Decreasing nitric oxide production from endothelial cells leads to the onset and progression of CVD.
(Adapted from Bryan et al., 2022)
There are various clinical studies on the role of L-arginine in managing hypertension. In a double-blind, placebo-controlled clinical trial, the effect of L-arginine supplements was assessed on flow-mediated brachial artery dilation in patients with hypertension. L-arginine supplementation (6g/L) significantly improved the flow-mediated dilation of the brachial artery compared to placebo5. In another clinical study, the effect of L-arginine on gestational hypertension was assessed. It was observed that L-arginine supplementation (20g/500 ml IV for 5 days followed by 4g OD for 2 weeks) significantly reduced systolic and diastolic blood pressure in the interventional group than placebo6. In a similar study, L-arginine supplementation significantly reduced systolic blood pressure and improved microvascular angina. Additionally, significant elevation in cGMP level was observed7. Another single-blind, controlled, cross-over study observed a significant improvement in blood pressure, creatinine clearance and reduction in blood glucose levels in individuals receiving an arginine-rich diet compared to the control8.
In conclusion, L-arginine could modulate blood pressure via nitric oxide production in endothelial cells. Thus, L-arginine supplements can be employed to effectively manage blood pressure.
References
(1) Oparil, S.; Acelajado, M. C.; Bakris, G. L.; Berlowitz, D. R.; Cífková, R.; Dominiczak, A. F.; Grassi, G.; Jordan, J.; Poulter, N. R.; Rodgers, A.; Whelton, P. K. Hypertension. Nature Reviews Disease Primers. Nature Publishing Group March 22, 2018. https://doi.org/10.1038/nrdp.2018.14.
(2) Stuehr, D. J. Arginine Metabolism: Enzymology, Nutrition, and Clinical Significance Enzymes of the L-Arginine to Nitric Oxide Pathway 1,2; 2004.
(3) Doulias, P. T.; Tenopoulou, M. Endothelial Nitric Oxide Synthase-Derived Nitric Oxide in the Regulation of Metabolism. F1000Research. F1000 Research Ltd 2020. https://doi.org/10.12688/f1000research.19998.1.
(4) Bryan, N. S. Nitric Oxide Deficiency Is a Primary Driver of Hypertension. Biochemical Pharmacology. Elsevier Inc. December 1, 2022. https://doi.org/10.1016/j.bcp.2022.115325.
(5) Lekakis, J. P.; Papathanassiou, S.; Papaioannou, T. G.; Papamichael, C. M.; Zakopoulos, N.; Kotsis, V.; Dagre, A. G.; Stamatelopoulos, K.; Protogerou, A.; Stamatelopoulos, S. F. Oral L-Arginine Improves Endothelial Dysfunction in Patients with Essential Hypertension. Int J Cardiol 2002, 86 (2), 317–323. https://doi.org/https://doi.org/10.1016/S0167-5273(02)00413-8.
(6) Facchinetti, F.; Saade, G. R.; Neri, I.; Pizzi, C.; Longo, M.; Volpe, A. L-Arginine Supplementation in Patients with Gestational Hypertension: A Pilot Study. Hypertens Pregnancy 2007, 26 (1), 121–130. https://doi.org/10.1080/10641950601147994.
(7) Palloshi, A.; Fragasso, G.; Piatti, P.; Monti, L. D.; Setola, E.; Valsecchi, G.; Galluccio, E.; Chierchia, S. L.; Margonato, A. Effect of Oral L-Arginine on Blood Pressure and Symptoms and Endothelial Function in Patients with Systemic Hypertension, Positive Exercise Tests, and Normal Coronary Arteries. Am J Cardiol 2004, 93 (7), 933–935. https://doi.org/https://doi.org/10.1016/j.amjcard.2003.12.040.
(8) Siani, A.; Pagano, E.; Iacone, R.; Iacoviello, L.; Scopacasa, F.; Strazzullo, P. Blood Pressure and Metabolic Changes During Dietary L-Arginine Supplementation in Humans; 2000; Vol. 13. https://academic.oup.com/ajh/article/13/5/547/103075.
