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Effects of inhaled nitric oxide on regional blood flow are consistent with intravascular nitric oxidedelivery
Open accessAbstract
Nitric oxide (NO) may be stabilized by binding to hemoglobin, by nitrosating thiol-containing plasma molecules, or by conversion to nitrite, all reactions potentially preserving its bioactivity in blood.Here we examined the contribution of blood-transported NO to regional vascular tone in humans before and during NO inhalation.While breathing room air and then room air with NO at 80 parts per million, forearm blood flow was measured in 16 subjects at rest and after blockade of forearm NO synthesis with N G -monomethyl-L-arginine (L-NMMA) followed by forearm exercise stress.L-NMMA reduced blood flow by 25% and increased resistance by 50%, an effect that was blocked by NO inhalation.With NO inhalation, resistance was significantly lower during L-NMMA infusion, both at rest and during repetitive hand-grip exercise.S-nitrosohemoglobin and plasma S-nitrosothiols did not change with NO inhalation.Arterial nitrite levels increased by 11% and arterial nitrosyl(heme)hemoglobin levels increased tenfold to the micromolar range, and both measures were consistently higher in the arterial than in venous blood.S-nitrosohemoglobin levels were in the nanomolar range, with no significant artery-to-vein gradients.These results indicate that inhaled NO during blockade of regional NO synthesis can supply intravascular NO to maintain normal vascular function.This effect may have application for the treatment of diseases characterized by endothelial dysfunction.
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“For example, the infusion of a competitive inhibitor of eNOS into the human systemic or coronary circulation decreases basal blood flow by ~25%”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [146]
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Cites
Furchgott, R. F., & Zawadzki, J. V. (1980) · Nature · doi:10.1038/288373a0 · Cited by 12,064
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
Vascular endothelial cells synthesize nitric oxide from L-arginine
Palmer, R. M. J., Ashton, D., & Moncada, S. (1988) · Nature · doi:10.1038/333664a0 · Cited by 4,786
Paradoxical 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
Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway
Otterbein, L. E., Bach, F. H., Alam, J., Soares, M., Tao Lu, H., Wysk, M., Davis, R. J., Flavell, R. A., & Choi, A. M. K. (2000) · Nature Medicine · doi:10.1038/74680 · Cited by 2,153
Inhaled Nitric Oxide for the Adult Respiratory Distress Syndrome
Rossaint, R., Falke, K. J., Lopez, F., Slama, K., Pison, U., & Zapol, W. M. (1993) · New England Journal of Medicine · doi:10.1056/nejm199302113280605 · Cited by 1,806
S-nitrosohaemoglobin: a dynamic activity of blood involved in vascular control
Jia, L., Bonaventura, C., Bonaventura, J., & Stamler, J. S. (1996) · Nature · doi:10.1038/380221a0 · Cited by 1,592
Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin.
Stamler, J. S., Jaraki, O., Osborne, J., Simon, D. I., Keaney, J., Vita, J., Singel, D., Valeri, C. R., & Loscalzo, J. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.16.7674 · Cited by 1,238
Ignarro, L. J., Byrns, R. E., Buga, G. M., & Wood, K. S. (1987) · Circulation Research · doi:10.1161/01.res.61.6.866 · Cited by 1,164
Inhaled nitric oxide. A selective pulmonary vasodilator reversing hypoxic pulmonary vasoconstriction
Frostell, C., Fratacci, M. D., Wain, J. C., Jones, R., & Zapol, W. M. (1991) · Circulation · doi:10.1161/01.cir.83.6.2038 · Cited by 1,128
Blood Flow Regulation by S -Nitrosohemoglobin in the Physiological Oxygen Gradient
Stamler, J. S., Jia, L., Eu, J. P., McMahon, T. J., Demchenko, I. T., Bonaventura, J., Gernert, K., & Piantadosi, C. A. (1997) · Science · doi:10.1126/science.276.5321.2034 · Cited by 1,050
Rees, D. D., Palmer, R. M. J., Hodson, H. F., & Moncada, S. (1989) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1989.tb11833.x · Cited by 850
Inhaled Nitric Oxide and Persistent Pulmonary Hypertension of the Newborn
Roberts, J. D., Fineman, J. R., Morin, F. C., Shaul, P. W., Rimar, S., Schreiber, M. D., Polin, R. A., Zwass, M. S., Zayek, M. M., Gross, I., et al. (1997) · New England Journal of Medicine · doi:10.1056/nejm199702273360902 · Cited by 800
Enzyme-independent formation of nitric oxide in biological tissues
Zweier, J. L., Wang, P., Samouilov, A., & Kuppusamy, P. (1995) · Nature Medicine · doi:10.1038/nm0895-804 · Cited by 788
Panza, J. A., Casino, P. R., Kilcoyne, C. M., & Quyyumi, A. A. (1993) · Circulation · doi:10.1161/01.cir.87.5.1468 · Cited by 707
Self-citationReactions between nitric oxide and haemoglobin under physiological conditions
Gow, A. J., & Stamler, J. S. (1998) · Nature · doi:10.1038/34402 · Cited by 562
Ichinose, F., Roberts, J. D., & Zapol, W. M. (2004) · Circulation · doi:10.1161/01.cir.0000134595.80170.62 · Cited by 540
Nitric oxide and iron proteins
Cooper, C. E. (1999) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(99)00021-3 · Cited by 510
Millar, T. M., Stevens, C. R., Benjamin, N., Eisenthal, R., Harrison, R., & Blake, D. R. (1998) · FEBS Letters · doi:10.1016/s0014-5793(98)00430-x · Cited by 491
Quyyumi, A. A., Dakak, N., Andrews, N. P., Husain, S., Arora, S., Gilligan, D. M., Panza, J. A., & Cannon, R. O. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117852 · Cited by 444
Self-citationGladwin, M. T., Shelhamer, J. H., Schechter, A. N., Pease-Fye, M. E., Waclawiw, M. A., Panza, J. A., Ognibene, F. P., & Cannon, R. O. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.21.11482 · Cited by 441
Self-citation[26] Oxidative reactions of hemoglobin
Winterbourn, C. C. (1990) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(90)86118-f · Cited by 411
Reduction of nitrite to nitric oxide catalyzed by xanthine oxidoreductase
Godber, B. L. J., Doel, J. J., Sapkota, G. P., Blake, D. R., Stevens, C. R., Eisenthal, R., & Harrison, R. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.11.7757 · Cited by 411
Non-Enzymatic Nitric Oxide Synthesis in Biological Systems
Zweier, J. L., Samouilov, A., & Kuppusamy, P. (1999) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(99)00018-3 · Cited by 363
Contribution of endothelium-derived nitric oxide to exercise-induced vasodilation.
Gilligan, D. M., Panza, J. A., Kilcoyne, C. M., Waclawiw, M. A., Casino, P. R., & Quyyumi, A. A. (1994) · Circulation · doi:10.1161/01.cir.90.6.2853 · Cited by 293
Self-citationInhaled Nitric Oxide in Acute Respiratory Distress Syndrome: A Pilot Randomized Controlled Study
Troncy, É., Collet, J., Shapiro, S., Guimond, J., Blair, L., Ducruet, T., Francœur, M., Charbonneau, M., & Blaise, G. A. (1998) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.157.5.9707090 · Cited by 293
Cooperativity in the dissociation of nitric oxide from hemoglobin.
Moore, E. G., & Gibson, Q. H. (1976) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)33557-3 · Cited by 292
Amezcua, J. L., Palmer, R. M. J., de Souza, B. M., & Moncada, S. (1989) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1989.tb12569.x · Cited by 276
Gladwin, M. T., Ognibene, F. P., Pannell, L. K., Nichols, J. S., Pease‐Fye, M. E., Shelhamer, J. H., & Schechter, A. N. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.180155397 · Cited by 269
Self-citationZhang, Z., Naughton, D., Winyard, P. G., Benjamin, N., Blake, D. R., & Symons, M. C. R. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9226 · Cited by 246
Fox-Robichaud, A., Payne, D., Hasan, S. U., Ostrovsky, L., Fairhead, T., Reinhardt, P., & Kubes, P. (1998) · Journal of Clinical Investigation · doi:10.1172/jci2736 · Cited by 227
Chu, A. C., Chambers, D. E., Lin, C., Kuehl, W. D., Palmer, R. M. J., Moncada, S., & Cobb, F. R. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115223 · Cited by 198
Evaluation of the Magnitude and Rate of Nitric Oxide Production from Nitrite in Biological Systems
Samouilov, A., Kuppusamy, P., & Zweier, J. L. (1998) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1998.0785 · Cited by 170
Dynamic state of S-nitrosothiols in human plasma and whole blood
Jourd’heuil, D., Hallén, K., Feelisch, M., & Grisham, M. B. (2000) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(99)00257-9 · Cited by 156
Contractile activity-induced adaptations in the mitochondrial protein import system
Takahashi, M. T., Chesley, A., Freyssenet, D. G., & Hood, D. A. (1998) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1998.274.5.c1380 · Cited by 139
Increased Nitrovasodilator Sensitivity in Endothelial Nitric Oxide Synthase Knockout Mice
Brandes, R. P., Kim, D.-Y., Schmitz-Winnenthal, F. H., Amidi, M., Gödecke, A., Mülsch, A., & Busse, R. (2000) · Hypertension · doi:10.1161/01.hyp.35.1.231 · Cited by 132
Gladwin, M. T., Schechter, A. N., Shelhamer, J. H., Pannell, L. K., Conway, D. A., Hrinczenko, B. W., Nichols, J. S., Pease‐Fye, M. E., Noguchi, C. T., Rodgers, G. P., et al. (1999) · Journal of Clinical Investigation · doi:10.1172/jci7637 · Cited by 131
Self-citationDevelopment of Chemiluminescence-Based Methods for Specific Quantitation of Nitrosylated Thiols
Samouilov, A., & Zweier, J. L. (1998) · Analytical Biochemistry · doi:10.1006/abio.1998.2609 · Cited by 127
Reductive Assays forS-Nitrosothiols: Implications for Measurements in Biological Systems
Fang, K., Ragsdale, N. V., Carey, R. M., Macdonald, T. L., & Gaston, B. M. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9688 · Cited by 127
Myoglobin O2 tension determined from measurement of carboxymyoglobin in skeletal muscle
Coburn, R. F., & Mayers, L. (1971) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1971.220.1.66 · Cited by 86
Extra-pulmonary effects of inhaled nitric oxide in swine with and without phenylephrine
Troncy, É., Francoeur, M., Salazkin, I., Yang, F., Charbonneau, M., Leclerc, G., Vinay, P., & Blaise, G. A. (1997) · British Journal of Anaesthesia · doi:10.1093/bja/79.5.631 · Cited by 76
Determination of PO2 and its heterogeneity in single capillaries
Zheng, L., Golub, A. S., & Pittman, R. N. (1996) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1996.271.1.h365 · Cited by 71
Ewing, J. F., & Janero, D. R. (1998) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(98)00083-5 · Cited by 64
Kermarrec, N., Zunic, P., Béloucif, S., Bénessiano, J., Drouet, L. O., & Payen, D. M. (1998) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.158.3.9709097 · Cited by 63
Influence of carbon monoxide on hemoglobin-oxygen binding
Hlastala, M. P., McKenna, H., Franada, R. L., & DETTER, J. C. (1976) · Journal of Applied Physiology · doi:10.1152/jappl.1976.41.6.893 · Cited by 62
Nitrosyl hemoglobin in blood of normoxic and hypoxic sheep during nitric oxide inhalation
Takahashi, Y. K., Kobayashi, H., Tanaka, N., Sato, T., Takizawa, N., & Tomita, T. (1998) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1998.274.1.h349 · Cited by 50
Inhaled NO impacts vascular but not extravascular compartments in postischemic peripheral organs
Kubes, P., Payne, D., Grisham, M. B., Jourd’heuil, D., & Fox‐Robichaud, A. (1999) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1999.277.2.h676 · Cited by 47
Half-Life of Blood Carboxyhemoglobin after Short-Term and Long-Term Exposure to Carbon Monoxide
Shimazu, T., Ikeuchi, H., Sugimoto, H., Goodwin, C. W., Mason, A. D., & Pruitt, B. A. (2000) · The Journal of Trauma: Injury, Infection, and Critical Care · doi:10.1097/00005373-200007000-00019 · Cited by 47
Liss, A. G., & Liss, P. (2000) · Plastic & Reconstructive Surgery · doi:10.1097/00006534-200005000-00022 · Cited by 33
Heterotropic Effectors Exert More Significant Strain on Monoligated than on Unligated Hemoglobin
Coletta, M., Angeletti, M., Ascone, I., Boumis, G., Castellano, A. C., Dell’Ariccia, M., Longa, S. D., Sanctis, G. D., Priori, A. M., Santucci, R., et al. (1999) · Biophysical Journal · doi:10.1016/s0006-3495(99)77312-1 · Cited by 16
Comparison of canine cardiovascular response to inhaled and intraperitoneally infused CO
Gutiérrez, G., Rotman, H. H., Reid, C. M., & Dantzker, D. R. (1985) · Journal of Applied Physiology · doi:10.1152/jappl.1985.58.2.558 · Cited by 12
Werner, B., & Lindahl, J. K. (1980) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.3109/00365518009092650 · Cited by 9
Sokal, J. A., Majka, J., & Palus, J. (1986) · PubMed · Cited by 3
Research works printed but not linked: 3
- Kubes, 1999, Am J Physiol, 277, H676
- Zheng, 1996, Am J Physiol, 271, H365
- Sokal, 1986, J Hyg Epidemiol Microbiol Immunol, 30, 57
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Lundberg, J. O., Weitzberg, E., & Gladwin, M. T. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2466 · Cited by 2,739
Self-citationRees, D. C., Williams, T. N., & Gladwin, M. T. (2010) · The Lancet · doi:10.1016/s0140-6736(10)61029-x · Cited by 2,504
Self-citationNitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation
Cosby, K., Partovi, K. S., Crawford, J. H., Patel, R. P., Reiter, C. D., Martyr, S., Yang, B. K., Waclawiw, M. A., Zalos, G., Xu, X., et al. (2003) · Nature Medicine · doi:10.1038/nm954 · Cited by 1,807
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Rother, R. P., Bell, L. B., Hillmen, P., & Gladwin, M. T. (2005) · JAMA · doi:10.1001/jama.293.13.1653 · Cited by 1,565
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Metadata
- Authors
- Cannon, R. O., Schechter, A. N., Panza, J. A., Ognibene, F. P., Pease-Fye, M. E., Waclawiw, M. A., Shelhamer, J. H., & Gladwin, M. T.
- Affiliations
- National Institutes of Health (US)
- National Institute of Diabetes and Digestive and Kidney Diseases (US)
- National Heart, Lung, and Blood Institute (US)
- Corresponding author
- Cannon, Richard O.
- Venue
- Journal of Clinical Investigation
- Published
- 2001-07-15
- Volume
- 108
- Issue
- 2
- Pages
- 279-287
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC203029
- OpenAlex
- W2161221991
- Cited by
- 298
- References
- 53
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 4 · 2023: 7 · 2022: 3 · 2021: 4 · 2020: 5 · 2019: 7 · 2018: 5 · 2017: 10 · 2016: 5 · 2015: 16 · 2014: 15 · 2013: 11 · 2012: 13
- FWCI
- 12.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology (medical) › 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 › Hemoglobin structure and function
- Keywords
- inhaled nitric oxide, regional blood flow, forearm blood flow, nitric oxide delivery, nitric oxide production, L-NMMA, nitric oxide synthase inhibition, vascular tone, nitrite, S-nitrosohemoglobin, S-nitrosothiols, endothelial dysfunction, handgrip exercise, vascular resistance
- MeSH terms
- Administration, Inhalation, Adult, Biological Transport, Endothelium, Vascular, Female, Forearm, Hemoglobins, Humans, Male, Mercaptoethanol, Middle Aged, Models, Chemical, Nitric Oxide, Nitrites, Nitroso Compounds, Regional Blood Flow, S-Nitrosothiols
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