ArticleAnesthesiology2010
Hyperglycemia adversely modulates endothelial nitric oxide synthase during anesthetic preconditioning through tetrahydrobiopterin- and heat shock protein 90-mediated mechanisms.
Article in Anesthesiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 48 citations in OpenAlex.
- Potential of imidazole derivatives in reducing vascular complications in experimental diabetes.Molecular and cellular biochemistry · 2026Article
- Anesthetic-mediated cardioprotection: from molecular mechanisms to clinical translation challenges.Frontiers in physiology · 2025Review
- Predictive modeling of ICU-AW inflammatory factors based on machine learning.BMC neurology · 2024Article
- Myocardial protection in cardiac surgery: a comprehensive review of current therapies and future cardioprotective strategies.Frontiers in medicine · 2024Review
- Measurement of Tetrahydrobiopterin in Animal Tissue Samples by HPLC with Electrochemical Detection-Protocol Optimization and Pitfalls.Antioxidants (Basel, Switzerland) · 2022Article
- Intensive Care Unit-Acquired Weakness: A Review of Recent Progress With a Look Toward the Future.Frontiers in medicine · 2020Review
- Sepiapterin alleviates impaired gastric nNOS function in spontaneous diabetic female rodents through NRF2 mRNA turnover and miRNA biogenesis pathway.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Insulin and Its Cardiovascular Effects: What Is the Current Evidence?Current diabetes reports · 2017Review
- Relationship between Glycemic Levels and Treatment Outcome among Critically Ill Children admitted into Emergency Room in Enugu.BMC pediatrics · 2017Article
- Isoflurane favorably modulates guanosine triphosphate cyclohydrolase-1 and endothelial nitric oxide synthase during myocardial ischemia and reperfusion injury in rats.Anesthesiology · 2015Article
- Anaesthetics as cardioprotectants: translatability and mechanism.British journal of pharmacology · 2015Review
- Cardioprotection during diabetes: the role of mitochondrial DNA.Anesthesiology · 2014Article
- Apolipoprotein A-1 mimetic D-4F enhances isoflurane-induced eNOS signaling and cardioprotection during acute hyperglycemia.American journal of physiology. Heart and circulatory physiology · 2013Article
- Diabetic cardiomyopathy: pathophysiology and clinical features.Heart failure reviews · 2013Review
- Impairment of endothelial-myocardial interaction increases the susceptibility of cardiomyocytes to ischemia/reperfusion injury.PloS one · 2013Article
- Resveratrol and diabetic cardiac function: focus on recent in vitro and in vivo studies.Journal of bioenergetics and biomembranes · 2012Review
- Glycemic control in critically ill patients.World journal of critical care medicine · 2012Review
- Impact of exercise and metabolic disorders on heat shock proteins and vascular inflammation.Autoimmune diseases · 2012Article
- Decreased tetrahydrobiopterin and disrupted association of Hsp90 with eNOS by hyperglycemia impair myocardial ischemic preconditioning.American journal of physiology. Heart and circulatory physiology · 2011Article
- Endothelial-cardiomyocyte crosstalk enhances pharmacological cardioprotection.Journal of molecular and cellular cardiology · 2011Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundEndothelial nitric oxide synthase activity is regulated by (6R-)5,6,7,8-tetrahydrobiopterin (BH4) and heat shock protein 90. The authors tested the hypothesis that hyperglycemia abolishes anesthetic preconditioning (APC) through BH4- and heat shock protein 90-dependent pathways.
methodsMyocardial infarct size was measured in rabbits in the absence or presence of APC (30 min of isoflurane), with or without hyperglycemia, and in the presence or absence of the BH4 precursor sepiapterin. Isoflurane-dependent nitric oxide production was measured (ozone chemiluminescence) in human coronary artery endothelial cells cultured in normal (5.5 mm) or high (20 mm) glucose conditions, with or without sepiapterin (10 or 100 microm).
resultsAPC decreased myocardial infarct size compared with control experiments (26 +/- 6% vs. 46 +/- 3%, respectively; P < 0.05), and this action was blocked by hyperglycemia (43 +/- 4%). Sepiapterin alone had no effect on infarct size (46 +/- 3%) but restored APC during hyperglycemia (21 +/- 3%). The beneficial actions of sepiapterin to restore APC were blocked by the nitric oxide synthase inhibitor N (G)-nitro-L-arginine methyl ester (47 +/- 2%) and the BH4 synthesis inhibitor N-acetylserotonin (46 +/- 3%). Isoflurane increased nitric oxide production to 177 +/- 13% of baseline, and this action was attenuated by high glucose concentrations (125 +/- 6%). Isoflurane increased, whereas high glucose attenuated intracellular BH4/7,8-dihydrobiopterin (BH2) (high performance liquid chromatography), heat shock protein 90-endothelial nitric oxide synthase colocalization (confocal microscopy) and endothelial nitric oxide synthase activation (immunoblotting). Sepiapterin increased BH4/BH2 and dose-dependently restored nitric oxide production during hyperglycemic conditions (149 +/- 12% and 175 +/- 9%; 10 and 100 microm, respectively).
conclusionThe results indicate that tetrahydrobiopterin and heat shock protein 90-regulated endothelial nitric oxide synthase activity play a central role in cardioprotection that is favorably modulated by volatile anesthetics and dysregulated by hyperglycemia. Enhancing the production of BH4 may represent a potential therapeutic strategy.
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