ArticleNitric oxide : biology and chemistry2007
Reduced neuronal nitric oxide synthase expression contributes to cardiac oxidative stress and nitroso-redox imbalance in ob/ob mice.
Article in Nitric oxide : biology and chemistry, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 54 citations in OpenAlex.
- Precision Medicine: Therapeutically Targeting Mitochondrial Alterations in Heart Failure.JACC. Basic to translational science · 2025Review
- Cardiometabolic Phenotype in HFpEF: Insights from Murine Models.Biomedicines · 2025Review
- Review
- Endothelial Dysfunction and Diabetic Cardiomyopathy.Frontiers in endocrinology · 2022Review
- Characterisation of the Myocardial Mitochondria Structural and Functional Phenotype in a Murine Model of Diabetic Cardiomyopathy.Frontiers in physiology · 2021Article
- S-Nitrosylation: An Emerging Paradigm of Redox Signaling.Antioxidants (Basel, Switzerland) · 2019Review
- SGLT2 inhibition with empagliflozin improves coronary microvascular function and cardiac contractility in prediabetic ob/obCardiovascular diabetology · 2019Article
- Activation of IGF-1 receptors and Akt signaling by systemic hyperinsulinemia contributes to cardiac hypertrophy but does not regulate cardiac autophagy in obese diabetic mice.Journal of molecular and cellular cardiology · 2017Article
- New Insights into the Immunobiology of Mononuclear Phagocytic Cells and Their Relevance to the Pathogenesis of Cardiovascular Diseases.Frontiers in immunology · 2017Review
- Nitric Oxide and Related Aspects Underlying Angina.The open cardiovascular medicine journal · 2017Review
- High-fat diet-induced obesity alters nitric oxide-mediated neuromuscular transmission and smooth muscle excitability in the mouse distal colon.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- Ischemic postconditioning protects the heart against ischemia-reperfusion injury via neuronal nitric oxide synthase in the sarcoplasmic reticulum and mitochondria.Cell death & disease · 2016Article
- Cardiac NO signalling in the metabolic syndrome.British journal of pharmacology · 2015Review
- Impaired Coronary and Renal Vascular Function in Spontaneously Type 2 Diabetic Leptin-Deficient Mice.PloS one · 2015Article
- Article
- NADPH oxidase-2 inhibition restores contractility and intracellular calcium handling and reduces arrhythmogenicity in dystrophic cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2014Article
- Resveratrol-enhanced autophagic flux ameliorates myocardial oxidative stress injury in diabetic mice.Journal of cellular and molecular medicine · 2014Article
- Protein kinase RNA-like endoplasmic reticulum kinase (PERK) signaling pathway plays a major role in reactive oxygen species (ROS)-mediated endoplasmic reticulum stress-induced apoptosis in diabetic cardiomyopathy.Cardiovascular diabetology · 2013Article
- Hydralazine and organic nitrates restore impaired excitation-contraction coupling by reducing calcium leak associated with nitroso-redox imbalance.The Journal of biological chemistry · 2013Article
- Multiple antioxidants improve cardiac complications and inhibit cardiac cell death in streptozotocin-induced diabetic rats.PloS one · 2013Article
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Disruption of leptin signaling in the heart may contribute to obesity-related cardiac disease, as leptin deficient (oblob) mice display cardiac hypertrophy, increased cardiac apoptosis and reduced survival. Since leptin maintains a tonic level of neuronal nitric oxide synthase (NOS1) expression in the brain, we hypothesized that leptin deficiency would decrease NOS1 cardiac expression, in turn activating xanthine oxidoreductase (XOR) and creating nitroso-redox imbalance. We studied 2- to 6-month-old oblob (n=26) and C57Bl/6 controls (n=27). Cardiac NOS1 protein abundance (P<0.01) and mRNA expression (P=0.03) were reduced in oblob (n=10 and 6, respectively), while NOS3 protein abundance and mRNA expression were unaltered. Importantly, cardiac NOS1 protein abundance was restored towards normal in oblob mice after leptin treatment (n=3; P<0.05 vs leptin untreated oblob mice). NO metabolite (nitrite and nitrate) production within the myocardium was also reduced in oblob mice (n=5; P=0.02). Furthermore, oxidative stress was increased in oblob mice as GSH/GSSG ratio was decreased (n=4; P=0.02). Whereas XOR activity measured by Amplex Red fluorescence was increased (n=8; P=0.04), XOR and NADPH oxidase subunits protein abundance were not changed in oblob mice (n=6). Leptin deficiency did not disrupt NOS1 subcellular localization, as NOS1 co-localized with ryanodine receptor but not with caveolin-3. In conclusion, leptin deficiency is linked to decreased cardiac expression of NOS1 and NO production, with a concomitant increase in XOR activity and oxidative stress, resulting in nitroso-redox imbalance. These data offer novel insights into potential mechanisms of myocardial dysfunction in obesity.
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