Regulation of nitric oxide production in health and disease

Center for Translational Research in Aging and Longevity, Donald W. Reynolds Institute on Aging, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
Current opinion in clinical nutrition and metabolic care 10/2009; 13(1):97-104. DOI: 10.1097/MCO.0b013e328332f99d
Source: PubMed


The purpose of this review is to highlight recent publications examining nitric oxide production in health and disease and its association with clinical nutrition and alterations in metabolism.
The role of the cofactor tetrahydrobiopterin in nitric oxide production and its relation with arginine availability is indicated as an important explanation for the arginine paradox. This offers potential for nitric oxide regulation by dietary factors such as arginine or its precursors and vitamin C. Because diets with a high saturated fat content induce high plasma fatty acid levels, endothelial nitric oxide production is often impaired due to a reduction in nitric oxide synthase 3 phosphorylation. Increasing the arginine availability by arginine therapy or arginase inhibition was, therefore, proposed as a potential therapy to treat hypertension. Recent studies in septic patients and transgenic mice models found that inadequate de-novo arginine production from citrulline reduces nitric oxide production. Citrulline supplementation may, therefore, be a novel therapeutic approach in conditions of arginine deficiency.
Both lack and excess of nitric oxide production in diseases can have various important implications in which dietary factors can play a modulating role. Future research is needed to expand our understanding of the regulation and adequate measurement of nitric oxide production at the organ level and by the different nitric oxide synthase isoforms, also in relation to clinical nutrition.

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Available from: Yvette C Luiking, Mar 12, 2015
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    • "Esta enzima, en presencia de oxígeno y NADPH, cataliza la síntesis de NO como co-producto de la transformación del aminoácido Larginia a L-citrulina. Existen 3 isoformas: neuronal (NOS 1), inducible (NOS 2) y endotelial (NOS 3), siendo esta última la isoforma de mayor relevancia en la respuesta al estrés hemodinámico (Luiking et al., 2010). Múltiples estudios han mostrado que el EF genera un aumento en la activación y expresión de eNOS, produciendo un incremento en la biodisponibilidad de NO endotelial (Yang et al., 2001; Rodríguez & González). "

    International Journal of Morphology 12/2015; 33(4):1348-1354. · 0.32 Impact Factor
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    • "arteries in humans is, at least in part, mediated by NO (Green et al., 2014). Furthermore, one of the enzymes that increases its expression in response to shear stress is NOS (Yee et al., 2008), specifically eNOS (Luiking et al., 2010). The use of NOS inhibitors, like L-NMMA or L-NAME, showed that the inhibition of NO synthesis suppresses the effect of shear stress on angiogenesis associated with muscular stimulation (Hudlicka et al., 2006) or placental microcirculation (Wieczorek et al., 1995). "
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    ABSTRACT: Physiological vascular function regulation is essential for cardiovascular health and depends on adequate control of molecular mechanisms triggered by endothelial cells in response to mechanical and chemical stimuli induced by blood flow. Endothelial dysfunction is one of the main risk factors of cardiovascular pathology, where the imbalance between the synthesis of vasodilator and vasoconstrictor molecules is common in the development of vascular disorders in systemic and placental circulation. In the placenta, an organ without autonomic innervations, the local control of vascular tone is critical for maintenance of fetal growth and mechanisms that underlie shear stress response induced by blood flow are essential during pregnancy. In this field, shear stress induced by moderate exercise is one of the most important mechanisms to improve vascular function through nitric oxide synthesis and stimulation of mechanical response of endothelial cells triggered by ion channels, caveolae, endothelial NO synthase, and vascular endothelial growth factor, among others. The demand for oxygen and nutrients by tissues and organs, especially in placentation and pregnancy, determines blood flow parameters, and physiological adaptations of vascular beds for covering metabolic requirements. In this regard, moderate exercise versus sedentarism shows potential benefits for improving vascular function associated with the enhancement of molecular mechanisms induced by shear stress. In this review, we collect evidence about molecular bases of physiological response to shear stress in order to highlight the relevance of moderate exercise-training for vascular health in adult and fetal life.
    Frontiers in Pharmacology 09/2014; 5. DOI:10.3389/fphar.2014.00209 · 3.80 Impact Factor
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    • "Nitric oxide (NO) is a short-lived pleiotropic regulator that plays a diverse variety of roles in living organisms. NO controls vascular tone and blood flow by inhibiting vascular smooth muscle contraction and growth, platelet aggregation, and leukocyte adhesion [1]. Moreover, NO mediates mitochondrial oxygen consumption through inhibition of cytochrome c oxidase [2]. "
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    ABSTRACT: In this study, we applied structure-based virtual screening techniques to identify natural product or natural product-like inhibitors of iNOS. The iNOS inhibitory activity of the hit compounds was characterized using cellular assays and an in vivo zebrafish larvae model. The natural product-like compound 1 inhibited NO production in LPS-stimulated Raw264.7 macrophages, without exerting cytotoxic effects on the cells. Significantly, compound 1 was able to reverse MPTP-induced locomotion deficiency and neurotoxicity in an in vivo zebrafish larval model. Hence, compound 1 could be considered as a scaffold for the further development of iNOS inhibitors for potential anti-inflammatory or anti-neurodegenerative applications.
    PLoS ONE 04/2014; 9(4):e92905. DOI:10.1371/journal.pone.0092905 · 3.23 Impact Factor
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