Cited by 139Cardiac Ischemia and ReperfusionNitric Oxide and Endothelin EffectsAldose Reductase and Taurine

Arginase inhibition mediates cardioprotection during ischaemia–reperfusion

Jung, C., Gonon, A. T., Sjoquist, P.-O., Lundberg, J. O., Pernow, J.·2010·Cardiovascular Research

Abstract

AIMS: Nitric oxide (NO) is vital for the integrity of the cardiovascular system and protection against ischaemic heart disease. Arginase is up-regulated during ischaemia-reperfusion (IR) and this enzyme might compete with NO synthase (NOS) for arginine. The present study investigated whether arginase blockade protects from myocardial IR injury and whether such an effect is coupled to increased NO bioavailability. METHODS AND RESULTS: Sprague-Dawley rats were subjected to 30 min of coronary artery ligation, followed by 2 h of reperfusion. The animals were given either saline, or the arginase inhibitor N-omega-hydroxy-nor-l-arginine (nor-NOHA) with or without the NO scavenger carboxy-2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (cPTIO) or the NOS inhibitor N(G)-monomethyl-l-arginine (l-NMMA) iv 15 min before ischaemia. The infarct size was 79 +/- 4% of the area at risk in the control group. Nor-NOHA treatment reduced the infarct size to 39 +/- 7% (P < 0.001). Administration of cPTIO or l-NMMA completely abolished the protective effect of nor-NOHA. Expression of arginase I was significantly (P < 0.05) increased in ischaemic myocardium. Nor-NOHA treatment resulted in higher plasma levels of nitrite (P < 0.05) and a 10-fold increase in the citrulline/ornithine ratio (P < 0.001), indicating a shift in arginine utilization towards NOS. CONCLUSION: Inhibition of arginase protects from myocardial infarction by a mechanism that is dependent on NOS activity and bioavailability of NO by shifting arginine utilization from arginase towards NOS. These findings suggest that targeting of arginase is a promising future therapeutic strategy for protection against myocardial IR injury.

Integrity signals

Registry

Crossref · 10.1093/cvr/cvp303

Cites

35 of 35 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Jung, C., Gonon, A. T., Sjoquist, P.-O., Lundberg, J. O., & Pernow, J.
Affiliations
  • Karolinska University Hospital (SE)
  • Karolinska Institutet (SE)
Corresponding author
Jung, C.
Venue
Cardiovascular Research
Published
2009-09-02
Volume
85
Issue
1
Pages
147-154
ISSN
0008-6363 (ISSN-L)
OpenAlex
W2019788114
Cited by
139
References
35
Citations by year
2026: 1 · 2025: 4 · 2024: 11 · 2023: 1 · 2022: 7 · 2021: 6 · 2020: 16 · 2019: 3 · 2018: 8 · 2017: 6 · 2016: 6 · 2015: 10 · 2014: 17 · 2013: 16 · 2012: 8
FWCI
6.11
Type
journal article
Language
en
Open access
closed
Locations
  • Cardiovascular Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Novo Nordisk
  • National Institutes of Health
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Aldose Reductase and Taurine
Keywords
arginase inhibition, myocardial ischemia-reperfusion injury, nitric oxide bioavailability, nitric oxide synthase, arginine utilization, nor-NOHA, cardioprotection, myocardial infarct size, nitrite, L-NMMA, cPTIO
MeSH terms
Amino Acids, Animals, Arginase, Arginine, Blood Pressure, Enzyme Inhibitors, Heart Rate, Male, Myocardial Infarction, Myocardium, Nitric Oxide, Nitrites, Myocardial Reperfusion Injury, Rats, Sprague-Dawley, Nitric Oxide Synthase, Rats

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