Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man
Abstract
NG monomethyl-L-arginine (L-NMMA), a specific inhibitor of the synthesis of endothelium-derived nitric oxide (NO), was infused into the brachial arteries of healthy volunteers to study the role of NO in the control of forearm blood flow. L-NMMA caused a 50% fall in basal blood flow and attenuated the dilator response to infused acetylcholine but not that to glyceryl trinitrate. These results indicate that the dilator action of endothelium-derived NO contributes to the control of basal and stimulated regional blood flow in man. Impairment of production of NO might account for the abnormalities in vascular reactivity that characterise a wide variety of disease states.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The endothelial isoform of nitric oxide synthase (eNOS) is responsible for the biosynthesis of NO in endothelial cells, which mediates vascular relaxation.
“The endothelial isoform of nitric oxide synthase (eNOS) is responsible for the biosynthesis of NO in endothelial cells which mediates vascular relaxation [146].”
From Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022) · cites this paper as [146]
Cites
Furchgott, R. F., & Zawadzki, J. V. (1980) · Nature · doi:10.1038/288373a0 · Cited by 12,064 · see citing works
Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor
Palmer, R. M. J., Ferrige, A. G., & Moncada, S. (1987) · Nature · doi:10.1038/327524a0 · Cited by 10,704 · see citing works
Self-citationVascular endothelial cells synthesize nitric oxide from L-arginine
Palmer, R. M. J., Ashton, D., & Moncada, S. (1988) · Nature · doi:10.1038/333664a0 · Cited by 4,745 · see citing works
Self-citationParadoxical Vasoconstriction Induced by Acetylcholine in Atherosclerotic Coronary Arteries
Ludmer, P. L., Selwyn, A. P., Shook, T., Wayne, R. R., Mudge, G. H., Alexander, R. W., & Ganz, P. (1986) · New England Journal of Medicine · doi:10.1056/nejm198610233151702 · Cited by 2,422 · see citing works
Role of endothelium-derived nitric oxide in the regulation of blood pressure.
Rees, D. D., Palmer, R. M. J., & Moncada, S. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.9.3375 · Cited by 1,827 · see citing works
Self-citationThe measurement of volume changes in human limbs
Whitney, R. J. (1953) · The Journal of Physiology · doi:10.1113/jphysiol.1953.sp004926 · Cited by 1,496 · see citing works
ENDOGENOUS NITRIC OXIDE INHIBITS HUMAN PLATELET ADHESION TO VASCULAR ENDOTHELIUM
Radomski, M. W., Palmer, R. M. J., & Moncada, S. (1987) · The Lancet · doi:10.1016/s0140-6736(87)91481-4 · Cited by 1,437 · see citing works
Self-citationFlow-induced release of endothelium-derived relaxing factor
Rubanyi, G. M., Romero, J. C., & Vanhoutte, P. (1986) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1986.250.6.h1145 · Cited by 1,373 · see citing works
Palmer, R. M. J., Rees, D. D., Ashton, D. S., & Moncada, S. (1988) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(88)81362-7 · Cited by 1,348 · see citing works
Self-citationThe Role of Endothelium in the Responses of Vascular Smooth Muscle to Drugs
Furchgott, R. F. (1984) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pa.24.040184.001135 · Cited by 937 · see citing works
The discovery of nitric oxide as the endogenous nitrovasodilator.
Moncada, S., Palmer, R. M. J., & Higgs, E. A. (1988) · Hypertension · doi:10.1161/01.hyp.12.4.365 · Cited by 493 · see citing works
Self-citationAisaka, K., Gross, S. S., Griffith, O. W., & Levi, R. (1989) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(89)92517-5 · Cited by 427 · see citing works
The loss of endothelium-dependent vascular relaxation in hypertension.
Lockette, W. E., Otsuka, Y., & Carretero, O. A. (1986) · Hypertension · doi:10.1161/01.hyp.8.6_pt_2.ii61 · Cited by 372 · see citing works
Shimokawa, H., & Vanhoutte, P. M. (1989) · Circulation Research · doi:10.1161/01.res.64.5.900 · Cited by 354 · see citing works
EDRF coordinates the behaviour of vascular resistance vessels
Griffith, T. M., Edwards, D. H., Davies, R. L., Harrison, T. J., & Evans, K. T. (1987) · Nature · doi:10.1038/329442a0 · Cited by 317 · see citing works
Kamata, K., Miyata, N., & Kasuya, Y. (1989) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1989.tb11993.x · Cited by 291 · see citing works
Whittle, B. J. R., López-Belmonte, J. L., & Rees, D. D. (1989) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1989.tb12639.x · Cited by 265 · see citing works
Vallance, P. J., COLLIER, J., & Moncada, S. (1989) · Cardiovascular Research · doi:10.1093/cvr/23.12.1053 · Cited by 243 · see citing works
Self-citationKilbom, Å., & Wennmalm, A. (1976) · The Journal of Physiology · doi:10.1113/jphysiol.1976.sp011358 · Cited by 200 · see citing works
Benjamin, N., Cockcroft, J. R., Collier, J., et al. (1989) · The Journal of Physiology · doi:10.1113/jphysiol.1989.sp017630 · Cited by 103 · see citing works
Self-citationDuff, F. A., Gc, P., & Whelan, R. F. (1955) · PubMed · Cited by 21 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure
Leone, A., Moncada, S., Vallance, P., Calver, A., & Collier, J. (1992) · The Lancet · doi:10.1016/0140-6736(92)90865-z · Cited by 2,107 · see citing works
Self-citationClose Relation of Endothelial Function in the Human Coronary and Peripheral Circulations
Anderson, T. J., Uehata, A., Gerhard, M. D., Meredith, I. T., Knab, S., Delagrange, D., Lieberman, E. H., Ganz, P., Creager, M. A., Yeung, A. C., et al. (1995) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(95)00327-4 · Cited by 2,033 · see citing works
Steinberg, H. O., Chaker, H., Leaming, R., Johnson, A., Brechtel, G., & Baron, A. D. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118709 · Cited by 1,687 · see citing works
Benavente-García, O., & Castillo, J. (2008) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf8006568 · Cited by 1,158 · see citing works
Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease
Ngo, V., & Duennwald, M. L. (2022) · Antioxidants · doi:10.3390/antiox11122345 · Cited by 1,130 · see citing works
Effect of exercise training on endothelium‐derived nitric oxide function in humans
Green, D. J., Maiorana, A., O'Driscoll, G., & Taylor, R. (2004) · The Journal of Physiology · doi:10.1113/jphysiol.2004.068197 · Cited by 1,040 · see citing works
Impaired nitric oxide-mediated vasodilation in patients with non-insulin-dependent diabetes mellitus
Williams, S. B., Cusco, J. A., Roddy, M.-A., Johnstone, M. T., & Creager, M. A. (1996) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(95)00522-6 · Cited by 1,014 · see citing works
McVeigh, G. E., Brennan, G. M., Johnston, G. D., McDermott, B. J., McGrath, L. T., Henry, W. R., Andrews, J. W., & Hayes, J. R. (1992) · Diabetologia · doi:10.1007/bf00429099 · Cited by 916 · see citing works
Endogenous nitric oxide synthesis: Biological functions and pathophysiology
Bredt, D. S. (1999) · Free Radical Research · doi:10.1080/10715769900301161 · Cited by 796 · see citing works
Hyperdynamic circulation in cirrhosis: A role for nitric oxide?
Vallance, P., & Moncada, S. (1991) · The Lancet · doi:10.1016/0140-6736(91)91384-7 · Cited by 615 · see citing works
Self-citationNitrogen oxide levels in patients after trauma and during sepsis
OCHOA, J. B., UDEKWU, A. O., BILLIAR, T. R., CURRAN, R. D., CERRA, F. B., SIMMONS, R. L., & PEITZMAN, A. B. (1991) · Annals of Surgery · doi:10.1097/00000658-199111000-00013 · Cited by 599 · see citing works
Vallance, P., & Leiper, J. (2004) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000128897.54893.26 · Cited by 553 · see citing works
Self-citationHibbs, J. B., Westenfelder, C., Taintor, R., Vavrin, Z., Kablitz, C., Baranowski, R. L., Ward, J. H., Menlove, R. L., McMurry, M. P., & Kushner, J. P. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115666 · Cited by 485 · see citing works
Biological significance of endogenous methylarginines that inhibit nitric oxide synthases
Leiper, J. (1999) · Cardiovascular Research · doi:10.1016/s0008-6363(99)00162-5 · Cited by 458 · see citing works
Taddei, S., Caraccio, N., Virdis, A., Dardano, A., Versari, D., Ghiadoni, L., Salvetti, A., Ferrannini, E., & Monzani, F. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030039 · Cited by 431 · see citing works
Panza, J. A., García, C. E., Kilcoyne, C. M., Quyyumi, A. A., & Cannon, R. O. (1995) · Circulation · doi:10.1161/01.cir.91.6.1732 · Cited by 428 · see citing works
Stimulation of the nitric oxide synthase pathway in human hepatocytes by cytokines and endotoxin
Nussler, A. K., Di Silvio, M., Billiar, T. R., Hoffman, R. A., Geller, D. A., Selby, R., Madariaga, J., & Simmons, R. L. (1992) · The Journal of Experimental Medicine · doi:10.1084/jem.176.1.261 · Cited by 420 · see citing works
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 · see citing works
Billiar, T. R., Curran, R. D., Harbrecht, B. G., Stuehr, D. J., Demetris, A. J., & Simmons, R. L. (1990) · Journal of Leukocyte Biology · doi:10.1002/jlb.48.6.565 · Cited by 335 · see citing works
Possible role of oxidative stress in the pathogenesis of hypertension
Ceriello, A. (2008) · Diabetes Care · doi:10.2337/dc08-s245 · Cited by 215 · see citing works
Hansel, T. T., Kharitonov, S. A., Donnelly, L. E., Erin, E. M., Currie, M. G., Moore, W. M., Manning, P. T., Recker, D. P., & Barnes, P. J. (2003) · The FASEB Journal · doi:10.1096/fj.02-0633fje · Cited by 208 · see citing works
Heitzer, T. (2001) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(01)00551-2 · Cited by 194 · see citing works
Bondonno, C. P., Liu, A. H., Croft, K. D., Considine, M. J., Puddey, I. B., Woodman, R. J., & Hodgson, J. M. (2015) · American Journal of Hypertension · doi:10.1093/ajh/hpu192 · Cited by 190 · see citing works
Joyner, M. J., Dietz, N. M., & Shepherd, J. T. (2001) · Journal of Applied Physiology · doi:10.1152/jappl.2001.91.6.2431 · Cited by 177 · see citing works
Higashi, Y., Sasaki, S., Nakagawa, K., Fukuda, Y., Matsuura, H., Oshima, T., & Chayama, K. (2002) · American Journal of Hypertension · doi:10.1016/s0895-7061(01)02317-2 · Cited by 173 · see citing works
Neuronal nitric oxide synthase and human vascular regulation
Melikian, N., Seddon, M. D., Casadei, B., Chowienczyk, P. J., & Shah, A. M. (2009) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2010.02.007 · Cited by 151 · see citing works
Lee-Young, R. S., Griffee, S. R., Lynes, S. E., Bracy, D. P., Ayala, J. E., McGuinness, O. P., & Wasserman, D. H. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.021048 · Cited by 145 · see citing works
Exercise-induced AMPK activity in skeletal muscle: Role in glucose uptake and insulin sensitivity
Friedrichsen, M., Mortensen, B., Pehmøller, C., Birk, J. B., & Wojtaszewski, J. F. P. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2012.06.013 · Cited by 143 · see citing works
Nitric oxide modulation of blood vessel tone identified by arterial waveform analysis
McVEIGH, G. E., ALLEN, P. B., MORGAN, D. R., HANRATTY, C. G., & SILKE, B. (2001) · Clinical Science · doi:10.1042/cs1000387 · Cited by 144 · see citing works
Dietary Nitrate, Nitric Oxide, and Cardiovascular Health
Bondonno, C. P., Croft, K. D., & Hodgson, J. M. (2016) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2013.811212 · Cited by 141 · see citing works
Skeletal muscle nNOSμ protein content is increased by exercise training in humans
McConell, G. K., Bradley, S. J., Stephens, T. J., Canny, B. J., Kingwell, B. A., & Lee-Young, R. S. (2007) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00796.2006 · Cited by 136 · see citing works
Effects of nitric oxide on the contraction of skeletal muscle
Maréchal, G., & Gailly, P. (1999) · Cellular and Molecular Life Sciences · doi:10.1007/s000180050359 · Cited by 135 · see citing works
Plasma nitric oxide levels in newborn infants with sepsis
Shi, Y., Li, H.-Q., Shen, C.-K., Wang, J.-H., Qin, S.-W., Liu, R., & Pan, J. (1993) · The Journal of Pediatrics · doi:10.1016/s0022-3476(05)81753-6 · Cited by 132 · see citing works
Neuronal Nitric Oxide Synthase Regulates Basal Microvascular Tone in Humans In Vivo
Seddon, M. D., Chowienczyk, P. J., Brett, S. E., Casadei, B., & Shah, A. M. (2008) · Circulation · doi:10.1161/circulationaha.107.744540 · Cited by 129 · see citing works
Higashi, Y. (2001) · American Journal of Hypertension · doi:10.1016/s0895-7061(01)02191-4 · Cited by 125 · see citing works
Stasch, J., Dembowsky, K., Perzborn, E., Stahl, E., & Schramm, M. (2002) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0704483 · Cited by 120 · see citing works
Anand, I. S., Chandrashekhar, Y., Wander, G. S., & Chawla, L. S. (1995) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(95)00007-q · Cited by 116 · see citing works
Regulation of skeletal muscle blood flow during exercise in ageing humans
Hearon, C. M., & Dinenno, F. A. (2016) · The Journal of Physiology · doi:10.1113/jp270593 · Cited by 107 · see citing works
Schmidlin, O., Forman, A., Leone, A., Sebastian, A., & Morris, R. C. (2011) · Hypertension · doi:10.1161/hypertensionaha.111.170175 · Cited by 82 · see citing works
Gee, L. C., & Ahluwalia, A. (2016) · Current Hypertension Reports · doi:10.1007/s11906-015-0623-4 · Cited by 80 · see citing works
How do fish oils affect vascular function?
Chin, J. P. F., & Dart, A. M. (1995) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.1995.tb01959.x · Cited by 77 · see citing works
L-Citrulline Reduces Time to Exhaustion and Insulin Response to a Graded Exercise Test
HICKNER, R. C., TANNER, C. J., EVANS, C. A., CLARK, P. D., HADDOCK, A., FORTUNE, C., GEDDIS, H., WAUGH, W., & MCCAMMON, M. (2006) · Medicine & Science in Sports & Exercise · doi:10.1249/01.mss.0000210197.02576.da · Cited by 77 · see citing works
Megson, I. L., Morton, S., Greig, I. R., Mazzei, F. A., Field, R. A., Butler, A. R., Caron, G., Gasco, A., Fruttero, R., & Webb, D. J. (1999) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0702346 · Cited by 49 · see citing works
Willoughby, D. S., Boucher, T., Reid, J., Skelton, G., & Clark, M. (2011) · International Journal of Sport Nutrition and Exercise Metabolism · doi:10.1123/ijsnem.21.4.291 · Cited by 36 · see citing works
Vanhatalo, A., L'Heureux, J. E., Black, M. I., Blackwell, J. R., Aizawa, K., Thompson, C., Williams, D. W., van der Giezen, M., Winyard, P. G., & Jones, A. M. (2025) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2025.07.002 · Cited by 15 · see citing works
- Authors
- Vallance, P., Collier, J., & Moncada, S.
- Affiliations
- St George's Hospital (GB)
- Wellcome Trust (GB)
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 1989-10
- Volume
- 334
- Issue
- 8670
- Pages
- 997-1000
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W2045138089
- Cited by
- 1,590
- References
- 21
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 12 · 2023: 11 · 2022: 19 · 2021: 18 · 2020: 18 · 2019: 16 · 2018: 12 · 2017: 18 · 2016: 16 · 2015: 29 · 2014: 31 · 2013: 35 · 2012: 25
- FWCI
- 39.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- nitric oxide, endothelium-derived nitric oxide, L-NMMA, peripheral arterial tone, forearm blood flow, brachial artery, acetylcholine, nitroglycerin, vasodilation, vascular reactivity, nitric oxide synthesis inhibition
- MeSH terms
- Acetylcholine, Adult, Arginine, Brachial Artery, Dose-Response Relationship, Drug, Drug Evaluation, Endothelium, Vascular, Female, Forearm, Nitroglycerin, Humans, Infusions, Intra-Arterial, Male, Muscle Tonus, Nitric Oxide, Regional Blood Flow, Time Factors, Vasodilation, omega-N-Methylarginine
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review