The ubiquitous role of nitric oxide in cardioprotection

Jones, Steven P.; Bolli, Roberto

doi:10.1016/j.yjmcc.2005.09.011

Cited by 434Cardiac Ischemia and ReperfusionNitric Oxide and Endothelin EffectsNeurological Disorders and Treatments

The ubiquitous role of nitric oxide in cardioprotection

Jones, Steven P., Bolli, Roberto·2006·Journal of Molecular and Cellular Cardiology

DOI 10.1016/j.yjmcc.2005.09.011

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Abstract

In recent years, major advances have been made toward understanding the role of nitric oxide (NO) in the ischemic biology of the heart. It is now clear that NO, either endogenous or exogenous, represents one of the most important defenses against myocardial ischemia-reperfusion injury. The purpose of this review is to provide an update on the cardioprotective actions of NO, with particular emphasis on the function of the inducible isoform of NO synthase (iNOS) and on the role of mitochondria in NO-mediated protection. This essay underscores some of the more prominent areas of ischemic biology that relate to NO, such as ischemic preconditioning, pharmacological cardioprotection, and gene therapy. The hypothesis that the late phase of preconditioning is mediated by increased iNOS activity resulting in enhanced NO bioavailability, first proposed by our group, is now widely accepted and can be regarded as a proven hypothesis. Likewise, the burgeoning field of postconditioning may share such a requirement for NO. Various drugs (e.g. statins, ACE inhibitors, angiotensin-receptor blockers, etc.) also produce salubrious effects in experimental models of myocardial infarction via their enhancement of NO bioavailability. Thus, NO appears to be a common mediator of the protection afforded by a wide array of seemingly unrelated pharmacological and nonpharmacological interventions, underscoring its fundamental role as a ubiquitous defense of the heart against ischemia and reperfusion. This review challenges the conventional wisdom that iNOS is deleterious during myocardial ischemia-reperfusion and instead proposes the concept that iNOS, when expressed in cardiac myocytes, is a profoundly protective protein. We also emphasize the emerging importance of the mitochondrial actions of NO. Although the precise molecular events remain to be defined, we propose that NO interacts with components of the electron transport chain and/or the mitochondrial permeability transition pore to limit post-ischemic myocardial damage, and that this action potentially provides a fundamental molecular explanation for the mechanism of NO-mediated cardioprotection.

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NOS ability to generate NO during ischemia is compromised because of the requirement for oxygen, BH4, and other co-factors that may be limiting during tissue ischemia.
“Although NO is known to protect tissues from ischemic injury, the ability of nitric oxide synthases to generate NO during ischemia is compromised because of the requirement for oxygen, BH4, and other co-factors which may be limiting during tissue ischemia [29–31].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [31]

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Sildenafil Citrate (Viagra) Induces Cardioprotective Effects after Ischemia/Reperfusion Injury in Infant Rabbits
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Nitric Oxide and Peroxynitrite in Health and Disease
Pacher, P., Beckman, J. S., & Liaudet, L. (2007) · Physiological Reviews · doi:10.1152/physrev.00029.2006 · Cited by 6,390 · see citing works
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Nitrite augments tolerance to ischemia/reperfusion injury via the modulation of mitochondrial electron transfer
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Preconditioning Results in S -Nitrosylation of Proteins Involved in Regulation of Mitochondrial Energetics and Calcium Transport
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Authors: Jones, S. P., & Bolli, R.
Affiliations: University of Louisville (US)
Corresponding author: Jones, Steven P.
ORCID: Jones, Steven P.
Bolli, Roberto
Venue: Journal of Molecular and Cellular Cardiology
Publisher: Elsevier BV
Published: 2006-01
Volume: 40
Issue: 1
Pages: 16-23
ISSN: 0022-2828 (ISSN-L)
DOI: 10.1016/j.yjmcc.2005.09.011
OpenAlex: W1966726553
Cited by: 434
References: 84
Citations by year: 2026: 1 · 2025: 2 · 2024: 5 · 2023: 6 · 2022: 7 · 2021: 17 · 2020: 8 · 2019: 6 · 2018: 20 · 2017: 16 · 2016: 14 · 2015: 17 · 2014: 22 · 2013: 24 · 2012: 35
FWCI: 25.85
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Journal of Molecular and Cellular Cardiology (publishedVersion)
PubMed (publishedVersion)
Funders: American Heart Association
National Institutes of Health
National Heart, Lung, and Blood Institute (P01HL078825, R01HL070897, HL 78825, HL 55757, HL-68088, HL70897, R01HL068088)
Topics: Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
Keywords: nitric oxide, cardioprotection, myocardial ischemia-reperfusion injury, inducible nitric oxide synthase, ischemic preconditioning, postconditioning, NO bioavailability, mitochondrial permeability transition pore, electron transport chain, statins, ACE inhibitors, angiotensin receptor blockers, gene therapy, myocardial infarction
MeSH terms: Animals, Heart, Humans, Mitochondria, Heart, Myocardial Infarction, Myocardium, Nitric Oxide, Nitrites, Ischemic Preconditioning, Myocardial, Protective Agents, Nitric Oxide Donors, Nitric Oxide Synthase Type II

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The ubiquitous role of nitric oxide in cardioprotection

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