The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
Nitric oxide promotes distant organ protection: Evidence for an endocrine role of nitric oxide
Open accessAbstract
Endothelial NOS (eNOS)-derived NO has long been considered a paracrine signaling molecule only capable of affecting nearby cells because of its short half-life in blood and relatively limited diffusion distance in tissues. To date, no studies have demonstrated that endogenously generated NO possesses a clearly defined endocrine function. Therefore, we evaluated whether enzymatic generation of NO in the heart is capable of modulating remote physiological actions and cell signaling. Mice with cardiac-specific overexpression of the human eNOS gene (CS-eNOS-Tg) were used to address this hypothesis. Cardiac-specific eNOS overexpression resulted in significant increases in nitrite, nitrate, and nitrosothiols in the heart, plasma, and liver. To examine whether the increase in hepatic NO metabolites could modulate cytoprotection, we subjected CS-eNOS-Tg mice to hepatic ischemia-reperfusion (I/R) injury. CS-eNOS-Tg mice displayed a significant reduction in hepatic I/R injury (4.2-fold reduction in the aminotransferase and a 3.5-fold reduction in aspartate aminotransferase) compared with WT littermates. These findings demonstrate that endogenously derived NO is transported in the blood, metabolized in remote organs, and mediates cytoprotection in the setting of I/R injury. This study presents clear evidence for an endocrine role of NO generated endogenously from eNOS and provides additional evidence for the profound cytoprotective actions of NO in the setting of I/R injury.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
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?
In the citing paper
“CS-eNOS-Tg mice displayed a significant protection against hepatic I/R injury due to the increase in hepatic NO metabolites originating from the myocardium.”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [164]
In the citing paper
“Elrod et al documented significant increases in nitrite, nitrate, and nitrosothiols in the heart, plasma, and liver [164].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [164]
In the citing paper
“Experiments also showed that pharmacological scavengers PTIO and NEM inhibited the protective effects in CS-eNOS-Tg mice, indicating a role for nitrite reduction to NO and S-nitrosylation for cytoprotection [164].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [164]
Citations
Cites
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 · cited 1×
“T discovery that a free-radical gas is endogenously generated and plays a profound role in cellular signaling and physiology (1, 2) has led to an intense effort toward elucidating the synthesis, storage, and transport of NO.”
BackgroundEndothelium-derived relaxing factor produced and released from artery and vein is nitric oxide.
Ignarro, L. J., Buga, G. M., Wood, K. S., Byrns, R. E., & Chaudhuri, G. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.24.9265 · Cited by 5,074
Ignarro, L. J., Lippton, H., Edwards, J. C., Baricos, W. H., Hyman, A. L., Kadowitz, P. J., & Gruetter, C. A. (1981) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)32738-2 · Cited by 1,633 · cited 1×
“This concept, although controversial, has long been speculated, with initial findings by Ignarro and colleagues (30) that nitrite-mediated vasodilation required thiols, and further suggesting the possibility of a RSNO intermediate (31) in NO-mediated physiology.”
BackgroundStamler, J. S., Simon, D. I., Osborne, J. A., Mullins, M. E., Jaraki, O., Michel, T. M., Singel, D. J., & Loscalzo, J. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.1.444 · Cited by 1,471
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
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
Control of coronary vascular tone by nitric oxide.
Kelm, M., & Schrader, J. (1990) · Circulation Research · doi:10.1161/01.res.66.6.1561 · Cited by 697
Endothelium‐derived nitric oxide: actions and properties
Ignarro, L. J. (1989) · The FASEB Journal · doi:10.1096/fasebj.3.1.2642868 · Cited by 679
Cytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver
Duranski, M. R., Greer, J. J. M., Dejam, A., Jaganmohan, S., Hogg, N., Langston, W., Patel, R. P., Yet, S.-F., Wang, X., Kevil, C. G., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci22493 · Cited by 674 · cited 2×
“Additionally, our laboratory and others (16, 17) have reported that nitrite can be consumed under ischemic/hypoxic conditions to yield NO and thus impede cellular injury.”
BackgroundSelf-citationInorganic nitrate is a possible source for systemic generation of nitric oxide
Lundberg, J. O., & Govoni, M. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.04.027 · Cited by 657
Cited by
Sorted by citations
Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation
Tejero, J., Shiva, S., & Gladwin, M. T. (2019) · Physiological Reviews · doi:10.1152/physrev.00036.2017 · Cited by 541
King, A. L., Polhemus, D. J., Bhushan, S., Otsuka, H., Kondo, K., Nicholson, C. K., Bradley, J., Islam, K. N., Calvert, J. W., Tao, Y., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1321871111 · Cited by 368
Self-citationKapil, V., Khambata, R. S., Jones, D. A., Rathod, K., Primus, C., Massimo, G., Fukuto, J. M., & Ahluwalia, A. (2020) · Pharmacological Reviews · doi:10.1124/pr.120.019240 · Cited by 248
Sindler, A. L., Fleenor, B. S., Calvert, J. W., Marshall, K. D., Zigler, M. L., Lefer, D. J., & Seals, D. R. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2011.00679.x · Cited by 218
Self-citationCalvert, J. W., Condit, M. E., Aragón, J. P., Nicholson, C. K., Moody, B. F., Hood, R. L., Sindler, A. L., Gundewar, S., Seals, D. R., Barouch, L. A., et al. (2011) · Circulation Research · doi:10.1161/circresaha.111.241117 · Cited by 207
Self-citation
Metadata
- Authors
- Elrod, J. W., Calvert, J. W., Gundewar, S., Bryan, N. S., & Lefer, D. J.
- Affiliations
- Albert Einstein College of Medicine (US)
- Departments of *Medicine and
- Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2008-08-12
- Volume
- 105
- Issue
- 32
- Pages
- 11430-11435
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2516252
- OpenAlex
- W2078820537
- Cited by
- 137
- References
- 41
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 8 · 2021: 2 · 2020: 3 · 2019: 4 · 2018: 3 · 2017: 7 · 2016: 4 · 2015: 11 · 2014: 7 · 2013: 15 · 2012: 24
- FWCI
- 8.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- American Heart Association
- National Institutes of Health
- National Heart, Lung, and Blood Institute (2R01 HL-060849, R01HL060849)
- National Institute of Diabetes and Digestive and Kidney Diseases (F32DK077380)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Ischemia and Reperfusion
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Keywords
- nitric oxide, endothelial nitric oxide synthase, hepatic ischemia-reperfusion injury, cytoprotection, nitrite/nitrate, S-nitrosothiols, hepatoprotection
- MeSH terms
- Animals, Biological Transport, Liver, Mice, Transgenic, Myocardium, Nitrates, Nitric Oxide, Nitrites, Organ Specificity, Reperfusion Injury, Cytoprotection, Paracrine Communication, Mice, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type III
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
