"Endothelial NOS and dietary L-arginine supplementation"
Sackler Faculty of Medicine, Tel-Aviv University
Published January 2, 1999
The study of Ohashi Y et al. (1) elegantly demonstrates reduced blood pressure in transgenic mice overexpressing bovine endothelial NOS (eNOS) in their vascular wall. This new study adds an important evidence for the crucial role for eNOS in hemodynamic control. However, the authors state that 'before this study, it was unclear if increasing eNOS expression in the intact circulatory system would actually augment production of NO or affect systemic hemodynamics'. This is a true, but incomplete, description of the relevant clinical research on the in vivo effects of eNOS modulation. Several human studies have demonstrated that increasing eNOS activity in vivo , via dietary supplementation with its essential amino-acid substrate, L-arginine, improves hemodynamics. For example, oral L-arginine (7x3 gr/day, 28 days) dramatically increased endothelium-dependent dilation in hypercholesterolemic young adults (2). Moreover, intracoronary administration of L-arginine mediated vasodilation in patients with coronary artery disease (3). A recent trial in patients with peripheral arterial occlusive disease showed that oral L-arginine (2X8 gr/day, 21 days) improved their pain-free walking distance by more than two-fold (4). This improvement correlated with increased urinary nitrate and cyclic GMP levels, indicating increased in vivo eNOS activity (4).
Together, these L-arginine trials suggest that dietary supplementation with the eNOS substrate could improve hemodynamics in several atherogenic and aging-related diseases, including (potentially) neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, where decreased cerebrospinal fluid nitrate levels could indicate reduced NO production (5). I would like to call upon the scientific community and the pharmaceutical industry to pursue the therapeutic potentials of L-arginine for treating hemodynamic deficiencies.
1. Ohashi Y, Kawashima S, Hirata Ki, Yamashita T, Ishida T, Inoue N, Sakoda T, Kurihara H, Yazaki Y, Yokoyama M. 1998. Hypotension and reduced nitric oxide- elicited vasorelaxation in transgenic Mice overexpressing endothelial nitric oxide synthase. J Clin Invest 102:2061-2071.
2. Clarkson P, Adams MR, Powe AJ, Donald AE, McCredie R, Robinson J, McCarthy SN, Keech A, Celermajer DS, Deanfield JE. 1996. Oral L-arginine improves endothelium-dependent dilation in hypercholesterolemic young adults. J Clin Invest 97:1989-1994.
3. Tousoulis D, Davies GJ, Tentolouris C, Crake T, Katsimaglis G, Stefanadis C, Toutouzas P. 1998. Effects of changing the availability of the substrate for nitric oxide synthase by L-arginine administration on coronary vasomotor tone in angina patients with angiographically narrowed and in patients with normal coronary arteries. Am J Cardiol. 82:1110-1113.
4. Boger RH, Bode-Boger SM, Thiele W, Creutzig A, Alexander K, Frolich JC. 1998. Restoring vascular nitric oxide formation by L-arginine improves the symptoms of intermittent claudication in patients with peripheral arterial occlusive disease. J Am Coll Cardiol 32:1336-1344.
5. Kuiper MA, Visser JJ, Bergmans PL, Scheltens P, Wolters EC. 1994. Decreased cerebrospinal fluid nitrate levels in Parkinson's disease, Alzheimer's disease and multiple system atrophy patients. J Neurol Sci 121:46-49.