The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
Randomized, Double-Blind, Placebo-Controlled Study of Supplemental Oral l -Arginine in Patients With Heart Failure
Abstract
Background Patients with heart failure have reduced peripheral blood flow at rest, during exercise, and in response to endothelium-dependent vasodilators. Nitric oxide formed from l -arginine metabolism in endothelial cells contributes to regulation of blood flow under these conditions. A randomized, double-blind crossover study design was used to determine whether supplemental oral l -arginine can augment peripheral blood flow and improve functional status in patients with moderate to severe heart failure. Methods and Results Fifteen subjects were given 6 weeks of oral l -arginine hydrochloride (5.6 to 12.6 g/d) and 6 weeks of matched placebo capsules in random sequence. Compared with placebo, supplemental oral l -arginine significantly increased forearm blood flow during forearm exercise, on average from 5.1±2.8 to 6.6±3.4 mL·min −1 ·dL −1 ( P <.05). Furthermore, functional status was significantly better on l -arginine compared with placebo, as indicated by increased distances during a 6-minute walk test (390±91 versus 422±86 m, P <.05) and lower scores on the Living With Heart Failure questionnaire (55±28 versus 42±26, P <.05). Oral l -arginine also improved arterial compliance from 1.99±0.38 to 2.36±0.30 mL/mm Hg ( P <.001) and reduced circulating levels of endothelin from 1.9±1.1 to 1.5±1.1 pmol/L ( P <.05). Conclusions Supplemental oral l -arginine had beneficial effects in patients with heart failure. Further studies are needed to confirm the therapeutic potential of supplemental oral l -arginine and to identify mechanisms of action in patients with heart failure.
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Cites
Furchgott, R. F., & Zawadzki, J. V. (1980) · Nature · doi:10.1038/288373a0 · Cited by 12,064
Vascular endothelial cells synthesize nitric oxide from L-arginine
Palmer, R. M. J., Ashton, D. S., & Moncada, S. (1988) · Nature · doi:10.1038/333664a0 · Cited by 4,769
Release of endothelin from the porcine aorta. Inhibition by endothelium-derived nitric oxide.
Boulanger, C., & Lüscher, T. F. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114477 · Cited by 1,045
Rector, T. S., & Cohn, J. N. (1992) · American Heart Journal · doi:10.1016/0002-8703(92)90986-6 · Cited by 1,018
Self-citationL-arginine improves endothelium-dependent vasodilation in hypercholesterolemic humans.
Creager, M. A., Gallagher, S. J., Girerd, X. J., Coleman, S. M., Dzau, V. J., & Cooke, J. P. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115987 · Cited by 813
Drexler, H., Zeiher, A. M., Meinzer, K., & Just, H. (1991) · The Lancet · doi:10.1016/0140-6736(91)92372-9 · Cited by 802
Endothelium-dependent vasodilation is attenuated in patients with heart failure.
Kubo, S. H., Rector, T. S., Bank, A. J., Williams, R. E., & Heifetz, S. M. (1991) · Circulation · doi:10.1161/01.cir.84.4.1589 · Cited by 775
Self-citationBittner, V. (1993) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1993.03510140062030 · Cited by 711
Antiatherogenic effects of L-arginine in the hypercholesterolemic rabbit.
Cooke, J. P., Singer, A. H., Tsao, P., Zera, P., Rowan, R. A., & Billingham, M. E. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115937 · Cited by 687
Evidence for endothelin-1-mediated vasoconstriction in severe chronic heart failure
Kiowski, W., Kim, J., Oechslin, E., Sütsch, G., Hunziker, P., Müller, P., Bertel, O., Schmitt, R., & Jones, R. (1995) · The Lancet · doi:10.1016/s0140-6736(95)91504-4 · Cited by 571
Cited by
Gluckman, T. J., Bhave, N. M., Allen, L. A., Chung, E. H., Spatz, E. S., Ammirati, E., Baggish, A. L., Bozkurt, B., Cornwell, W. K., Harmon, K. G., et al. (2022) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2022.02.003 · Cited by 389
Schulman, S. P., Becker, L. C., Kass, D. A., Champion, H. C., Terrin, M. L., Forman, S., Ernst, K. V., Kelemen, M. D., Townsend, S. N., Capriotti, A., et al. (2006) · JAMA · doi:10.1001/jama.295.1.58 · Cited by 357
The l-arginine paradox: Importance of the l-arginine/asymmetrical dimethylarginine ratio
BODEBOGER, S., SCALERA, F., & IGNARRO, L. (2007) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2007.03.002 · Cited by 347
The Clinical Pharmacology of L-Arginine
Böger, R. H., & Bode-Böger, S. M. (2001) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.41.1.79 · Cited by 331
Arginine Therapy: A New Treatment for Pulmonary Hypertension in Sickle Cell Disease?
Morris, C. R., Morris, S. M., Hagar, W., van Warmerdam, J., Claster, S., Kepka-Lenhart, D., Machado, L., Kuypers, F. A., & Vichinsky, E. P. (2003) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200208-967oc · Cited by 329
Metadata
- Authors
- Rector, T. S., Bank, A. J., Mullen, K. A., Tschumperlin, L. K., Sih, R., Pillai, K., & Kubo, S. H.
- Venue
- Circulation
- Published
- 1996-06-15
- Volume
- 93
- Issue
- 12
- Pages
- 2135-2141
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W1990771731
- Cited by
- 275
- References
- 42
- FWCI
- 5.79
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Randomized, Double-Blind, Placebo-Controlled Study of Supplemental Oral l -Arginine in Patients With Heart Failure. https://app.cochat.ai/papers/10.1161/01.cir.93.12.2135
- The paper
- Rector, T. S., Bank, A. J., Mullen, K. A., Tschumperlin, L. K., Sih, R., Pillai, K., & Kubo, S. H. (1996). Randomized, Double-Blind, Placebo-Controlled Study of Supplemental Oral l -Arginine in Patients With Heart Failure. Circulation. https://doi.org/10.1161/01.cir.93.12.2135
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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