Enhanced S -Nitroso-Albumin Formation From Inhaled NO During Ischemia/Reperfusion
Abstract
In the present study, we investigated whether inhaled nitric oxide (NO) was transported by plasma proteins, such as S-nitroso-albumin (SNO-Alb), in the feline circulation and whether this molecule delivers NO to the periphery under conditions of stress, specifically ischemia/reperfusion (I/R). A flow probe was interposed between the femoral and superior mesenteric artery for blood flow measurements, and a branch of the superior mesenteric vein was cannulated for arterial-venous sampling. In animals breathing room air, SNO-Alb was below detection level in arterial or venous blood. NO inhalation resulted in a significant arterial-venous gradient for SNO-Alb. Concomitant with this loss of SNO-Alb across the intestinal vasculature was an increase in nitrite (NO2-). However, this release of NO was not sufficient to alter intestinal blood flow. I/R during NO inhalation caused a very large increase in arterial SNO-Alb that permitted a 5-fold increase in SNO-Alb consumption and significant generation of NO2- within the postischemic intestinal vasculature. The increased SNO-Alb consumption was sufficient to dramatically improve intestinal blood flow. The very large burst of arterial SNO-Alb during I/R was completely blocked by the administration of superoxide dismutase, suggesting that oxidative stress contributed to the increased SNO-Alb formation. Our data suggest that inhaled NO can increase nitrosothiol production and these molecules may be a functional NO delivery system during cardiovascular disease.
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Nitrite reduction back to NO under appropriate pathophysiological conditions can generate many nitroso species, or nitrite itself may mediate intracellular nitrosation reactions such as RSNO formation.
“Recent studies show the potential role of nitrite reduction back to NO under appropriate pathophysiological conditions to generate many nitroso species or that nitrite itself may mediate intracellular nitrosation reactions (e.g. RSNO formation) [22, 23].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [23]
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Nitrosothiol stores in vascular tissue: Modulation by ultraviolet light, acetylcholine and ionomycin
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“Furthermore, changes in the levels of nitrite, the major oxidative breakdown product of nitric oxide in biological fluids in the absence of hemoglobin (Lauer et al., 2002; Ng et al., 2004), served to indicate that nitric oxide was released from tissues and cells in our experimental protocols.”
BackgroundMethodInfluentialZhang, L., Croix, C. M. S., Cao, R., Wasserloos, K., Watkins, S. C., Stevens, T., Li, S., Tyurin, V. A., Kagan, V. E., & Pitt, B. R. (2006) · Experimental Biology and Medicine · doi:10.1177/153537020623100909 · Cited by 29 · see citing works
Emerging role of nitrite in myocardial protection
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“, 1998), 4) increase intestinal blood flow during concurrent NO synthase inhibition or after intestinal ischemia-reperfusion injury in cats (Fox-Robichaud et al., 1998; Kubes et al., 1999; Ng et al., 2004), 5) prevent forearm vasoconstriction during regional NO synthase inhibition in human volunteers (Rassaf et al.”
BackgroundMaher, A. R., Arif, S., Madhani, M., Abozguia, K., Ahmed, I., Fernandez, B. O., Feelisch, M., O'Sullivan, A., Christopoulos, A., Sverdlov, A. L., et al. (2013) · British Journal of Pharmacology · doi:10.1111/bph.12152 · Cited by 26 · see citing works
“…being indicative of NO generation and therefore indicative of diminished eNOS activity in CHF (Lauer et al., 2001), whereas RXNO concentrations reflect the generation of S-nitrosoproteins from either NO or NO2- (Bryan et al., 2005), as well as a measure of prevalent redox stress (Ng et al., 2004).”
BackgroundRoutes for Formation of S-Nitrosothiols in Blood
Nagababu, E., & Rifkind, J. M. (2011) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-011-9321-2 · Cited by 25 · see citing works
“In spite of these kinetic constraints, reports indicate the formation of RSNO in plasma following the incubation of NO donors with whole blood [42], intravenous infusion of NO in human subjects [44], inhalation of NO [43, 98], and”
BackgroundWang, Q., Akhavan, B., Jing, F., Cheng, D., Sun, H. L., Xie, D., Leng, Y. X., Bilek, M., & Huang, N. (2018) · Advanced Materials Interfaces · doi:10.1002/admi.201701487 · Cited by 24 · see citing works
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Nitric oxide facilitates the targeting Kupffer cells of a nano-antioxidant for the treatment of NASH
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Can Nitric Oxide–Based Therapy Prevent Bronchopulmonary Dysplasia?
Raffay, T. M., Martin, R. J., & Reynolds, J. D. H. (2012) · Clinics in Perinatology · doi:10.1016/j.clp.2012.06.011 · Cited by 18 · see citing works
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Bonder, C. S., Knight, D., Hernández-Saavedra, D., McCord, J. M., & Kubes, P. (2004) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00049.2004 · Cited by 17 · see citing works
“This dose of 1 U/g body wt was chosen on the basis of previous reports that these protocols were efficacious in vivo in other inflammatory models (5, 9, 16, 39).”
MethodInhaled nitric oxide does not reduce systemic vascular resistance in mice
Hataishi, R., Zapol, W. M., Bloch, K. D., & Ichinose, F. (2005) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00938.2005 · Cited by 16 · see citing works
“While our current results do not suggest that enough NO or NO adducts reach the periphery to cause vasodilation, these findings are not surprising in light of recent reports by Ng and colleagues (11), who found that mesenteric I/R, but not NOS inhibition by L-NAME, was associated with sufficient production and consump…”
ResultBohlen, H. G. (2012) · Microcirculation · doi:10.1111/micc.12003 · Cited by 15 · see citing works
“Measurements of S-nitrosothiol compounds have used light and chemical measurement assays rather than NO-sensitive electrodes [18,25,28,29,31,32].”
BackgroundMethodSummary: Systemic Effects of Inhaled Nitric Oxide
Gaston, B. M. (2006) · Proceedings of the American Thoracic Society · doi:10.1513/pats.200506-049bg · Cited by 15 · see citing works
“More recently, Ng and coworkers ( 9 ) have gone back to this model of the effect of inhaled NO on mesenteric ischemia to investigate the mechanism by which the systemic effect is caused.”
BackgroundS -Nitrosoalbumin and Other S -Nitrosothiols in the Blood: Is Their Quantity of No Relevance?
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Nitric Oxide and the Cardiovascular System
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Sustained lung activity of a novel chimeric protein, SOD2/3, after intratracheal administration
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Stojanović, I. R., Djordjević, G., Pavlović, R., Djordjević, V. B., Pavlovic, D. D., Cvetković, T., Ljubisavljević, S., Bašić, J., & Zabar, K. (2012) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2012.09.026 · Cited by 11 · see citing works
“In addition, reactive oxygen species, have been found to potentiate albumin S-nitrosylation [35].”
BackgroundNitric oxide and thiols: Chemical biology, signalling paradigms and vascular therapeutic potential
Dent, M. R., & DeMartino, A. W. (2023) · British Journal of Pharmacology · doi:10.1111/bph.16274 · Cited by 10 · see citing works
“S -Nitrosated species (both proteins and/or small molecules) have been proposed to contribute to this systemic signalling during iNO treatment (McMahon & Doctor, 2006; Ng et al., 2004).”
Conahey, G. R., Power, G. G., Hopper, A. O., Terry, M. H., Kirby, L. S., & Blood, A. B. (2008) · Pediatric Research · doi:10.1203/pdr.0b013e318180f08b · Cited by 9 · see citing works
“Other possibilities include s-nitrosated proteins (RSNOs) (28,29), and iron-nitrosyl Hb, HbNO (5).”
BackgroundRole of nitric oxide in liver transplantation: Should it be routinely used?
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Interaction between albumin-bound dinitrosyl iron complexes and reactive oxygen species
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Extrapulmonary Effects of Inhaled Nitric Oxide
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“Increased levels of these thiols have been shown with the use of inhaled NO. 153,154 These molecules will demonstrate vasoac-tivity in states of relative NO de fi ciency but are not dependent on hypoxia.”
The effect of inhaled nitric oxide on splanchnic perfusion in a neonatal piglet model
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“Methods of quantification of RSNOs The ideal method to quantify RSNOs is a method that i) has a LOD in the nanomolar range in order to detect LMW- RSNOs and in the micromolar range in order to HMW-RSNOs, ii) is selective to NO (no detection of nitrite or other biological molecule), iii) that does not underor over-esti…”
BackgroundInfluentialInvestigating the role of nitric oxide clones in cardiovascular conditions
Arif, S. (2014) · University of Birmingham Institutional Research Archive (University of Birmingham)
- Authors
- Ng, E. S. M., Jourd’heuil, D., McCord, J. M., Hernandez, D., Yasui, M., Knight, D., & Kubes, P.
- Affiliations
- University of Calgary (CA)
- From the Department of Physiology and Biophysics (E.S.M.N., D.K., P.K.), Immunology Research Group, University of Calgary, Calgary, Alberta, Canada; Center for Cardiovascular Sciences (D.J.), Albany Medical College, Albany, NY; and Webb-Waring Institute (J.M.M., D.H., M.Y.), University of Colorado Health Sciences Center, Denver, Colo.
- Venue
- Circulation Research
- Published
- 2004-03-05
- Volume
- 94
- Issue
- 4
- Pages
- 559-565
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2096856230
- Cited by
- 97
- References
- 40
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 1 · 2021: 2 · 2020: 1 · 2018: 2 · 2017: 2 · 2016: 4 · 2015: 7 · 2014: 4 · 2013: 2 · 2012: 8
- FWCI
- 7.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canada Research Chairs
- Canadian Institutes of Health Research
- National Cancer Institute (CA-89366, R01CA089366)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- inhaled nitric oxide, ischemia-reperfusion, nitric oxide delivery, S-nitrosothiols, nitrite, intestinal blood flow, oxidative stress, superoxide dismutase, superior mesenteric artery, superior mesenteric vein, feline model
- MeSH terms
- Administration, Inhalation, Animals, Biological Transport, Cats, Constriction, Intestines, Ischemia, Nitric Oxide, Nitrites, Nitroso Compounds, Oxidation-Reduction, Recombinant Fusion Proteins, Serum Albumin, Bovine, Splanchnic Circulation, Superoxides, Superoxide Dismutase, Vasodilation, Reperfusion, Mesenteric Artery, Superior, Oxidative Stress, NG-Nitroarginine Methyl Ester, Nitric Oxide Donors, S-Nitrosoglutathione
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