ArticleClinical Medicine Insights. Cardiology2018
Citrulline Improves Early Post-Ischemic Recovery or Rat Hearts In Vitro by Shifting Arginine Metabolism From Polyamine to Nitric Oxide Formation.
Article in Clinical Medicine Insights. Cardiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 13 citations in OpenAlex.
- L-Citrulline Supplementation Reduces Blood Pressure and Myocardial Infarct Size under Chronic Intermittent Hypoxia, a Major Feature of Sleep Apnea Syndrome.Antioxidants (Basel, Switzerland) · 2022Article
- Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Deletion but Not Inhibition of Extracellular PCSK9 Reduces Infarct Sizes Ex Vivo but Not In Vivo.International journal of molecular sciences · 2022Article
- Mitochondria Isolated from Hearts Subjected to Ischemia/Reperfusion Benefit from Adenine Nucleotide Translocase 1 Overexpression.Membranes · 2021Article
- Implications of Oxidative and Nitrosative Post-Translational Modifications in Therapeutic Strategies against Reperfusion Damage.Antioxidants (Basel, Switzerland) · 2021Review
- Semantic Multi-Classifier Systems Identify Predictive Processes in Heart Failure Models across Species.Biomolecules · 2018Article
- L-citrulline increases arginase II protein levels and arginase activity in hypoxic piglet pulmonary artery endothelial cells.Pulmonary circulationArticle
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundReperfusion or reopening of occluded vessels is the gold standard to terminate ischemia. However, early functional recovery after reperfusion is often low requiring inotropic intervention. Although catecholamines increase inotropy and chronotropy, they are not the best choice because they increase myocardial oxygen and substrate demand. As nitric oxide (NO) contributes to cardiac function, we tested the hypothesis that addition of citrulline during the onset of reperfusion improves post-ischemic recovery because citrulline can reenter arginine consumption of NO synthases (NOS) but not of arginases.
methodsHearts from adult rats were used in this study, exposed to 45-minute global ischemia and subsequently reperfused for 180 minutes. Citrulline (100 µM) or arginine (100 µM) was added with reperfusion and remained in the perfusion buffer for 180 minutes. Nω-nitro-l-arginine methyl ester (l-NAME) was used to antagonize NOS activity.
resultsCitrulline increased load-free cell shortening of isolated adult rat cardiomyocytes and improved left ventricular developed pressure (LVDP) under normoxic conditions, indicating that citrulline can affect heart function. Ischemia/reperfusion caused a constitutive loss of function during 3 hours of reperfusion, whereas citrulline, but not arginine, improved the functional recovery during reperfusion. This effect was attenuated by co-administration of l-NAME. Although citrulline increased the formation of nitrite, l-NAME attenuated this effect indicating again a positive effect of citrulline on NO formation. Citrulline, but not arginine, increased the expression of arginase-1 (protein and mRNA) but l-NAME attenuated this effect again. Collectively, citrulline improved the post-ischemic recovery in an NO-dependent way.
conclusionsCitrulline, known to block arginase and to support NO formation, improves the early functional recovery of post-ischemic hearts and may be an alternative to catecholamines to improve early post-ischemic recovery.
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