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Impact of the L-arginine-Nitric Oxide Pathway and Oxidative Stress on the Pathogenesis of the Metabolic Syndrome.

C R A, T M C B, C M, A C R, A C MR - Open Biochem J (2008)

Bottom Line: It occurs in genetically susceptible individuals with environmental influences and has serious economic and social consequences.Pharmacological and non-pharmacological therapies should be individualized and targeted to normalize its alterations of blood pressure, HDL cholesterol, triglycerides and glucose values.Emerging evidence is available that NO, inflammation and oxidative stress play important roles in the physiopathology of this syndrome.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Farmacologia e Psicobiologia, Instituto de Biologia, Av. 28 de Setembro 87 CEP 20551-030, Rio de Janeiro, Brazil.

ABSTRACT
The discovery of the physiological roles of nitric oxide has revolutionized the understanding of regulation of vascular tone, platelet adhesion and aggregation, and immune activation. Perhaps the most intriguing aspect of nitric oxide (NO) is that it is a gas that, in the absence of receptors, can regulate both normal physiological events and mediate cytotoxicity under pathological conditions. NO is produced from L-arginine by NO synthases (NOS), yielding L-citrulline and NO. The regulation of L-arginine pathway activity occurs at the level of NO production. The metabolic syndrome is a cluster of insulin resistance, elevated blood pressure, and atherogenic dyslipidemia, a common basis of cardiovascular disease. It occurs in genetically susceptible individuals with environmental influences and has serious economic and social consequences. Pharmacological and non-pharmacological therapies should be individualized and targeted to normalize its alterations of blood pressure, HDL cholesterol, triglycerides and glucose values. Despite the increasing prevalence of the metabolic syndrome in the last decades, there has been little progress in the understanding of the precise mechanisms involved in the pathogenesis of this syndrome and its complications. Emerging evidence is available that NO, inflammation and oxidative stress play important roles in the physiopathology of this syndrome. This review summarizes and evaluates the participation of the L-arginine-NO pathway and oxidative stress in the physiopathology of the metabolic syndrome and cardiovascular events at the systemic level, as well as the effects of exercise on this syndrome.

No MeSH data available.


Related in: MedlinePlus

NO=nitric oxide; eNOS= endothelial nitric oxide synthase.
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Figure 2: NO=nitric oxide; eNOS= endothelial nitric oxide synthase.

Mentions: The pathophysiology of the metabolic syndrome remains a subject of continuing controversy. There are studies suggesting that insulin resistance is of central importance in this syndrome. One third of an apparently healthy population is sufficiently insulin resistant to develop significant clinical disease [27, 28]. Insulin resistance has traditionally been defined from a glucocentric view—i.e., when a defect in insulin action results in fasting hyperinsulinaemia to maintain euglycaemia [4]. Insulin has important vascular actions to stimulate production of NO in endothelium, leading to increased blood flow that contributes significantly to insulin-mediated glucose uptake. Insulin signaling pathways in the vascular endothelium regulating production of NO share striking similarities with metabolic insulin signaling pathways in skeletal muscle and adipose tissue [29]. Defective insulin-stimulated endothelial release of NO appears to be responsible, in part, for impaired capillary network expansion and the inability of insulin to redirect blood flow in the microcirculation towards metabolically active tissues (Fig. 2). As a result, the diffusion of insulin and its metabolic substrates is delayed and diminished, further aggravating the underlying insulin resistance. Moreover, the major factor in determining the rate of insulin transport across the capillary bed must be the size of the capillary bed itself or the inability of insulin to recruit previously closed capillary beds. In addition to insulin, adipocytokines and other endothelial products have been identified in insulin resistant obese individuals that are capable of altering capillary permeability, and thus could also interfere with the insulin’s metabolic action [30].


Impact of the L-arginine-Nitric Oxide Pathway and Oxidative Stress on the Pathogenesis of the Metabolic Syndrome.

C R A, T M C B, C M, A C R, A C MR - Open Biochem J (2008)

NO=nitric oxide; eNOS= endothelial nitric oxide synthase.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2570556&req=5

Figure 2: NO=nitric oxide; eNOS= endothelial nitric oxide synthase.
Mentions: The pathophysiology of the metabolic syndrome remains a subject of continuing controversy. There are studies suggesting that insulin resistance is of central importance in this syndrome. One third of an apparently healthy population is sufficiently insulin resistant to develop significant clinical disease [27, 28]. Insulin resistance has traditionally been defined from a glucocentric view—i.e., when a defect in insulin action results in fasting hyperinsulinaemia to maintain euglycaemia [4]. Insulin has important vascular actions to stimulate production of NO in endothelium, leading to increased blood flow that contributes significantly to insulin-mediated glucose uptake. Insulin signaling pathways in the vascular endothelium regulating production of NO share striking similarities with metabolic insulin signaling pathways in skeletal muscle and adipose tissue [29]. Defective insulin-stimulated endothelial release of NO appears to be responsible, in part, for impaired capillary network expansion and the inability of insulin to redirect blood flow in the microcirculation towards metabolically active tissues (Fig. 2). As a result, the diffusion of insulin and its metabolic substrates is delayed and diminished, further aggravating the underlying insulin resistance. Moreover, the major factor in determining the rate of insulin transport across the capillary bed must be the size of the capillary bed itself or the inability of insulin to recruit previously closed capillary beds. In addition to insulin, adipocytokines and other endothelial products have been identified in insulin resistant obese individuals that are capable of altering capillary permeability, and thus could also interfere with the insulin’s metabolic action [30].

Bottom Line: It occurs in genetically susceptible individuals with environmental influences and has serious economic and social consequences.Pharmacological and non-pharmacological therapies should be individualized and targeted to normalize its alterations of blood pressure, HDL cholesterol, triglycerides and glucose values.Emerging evidence is available that NO, inflammation and oxidative stress play important roles in the physiopathology of this syndrome.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Farmacologia e Psicobiologia, Instituto de Biologia, Av. 28 de Setembro 87 CEP 20551-030, Rio de Janeiro, Brazil.

ABSTRACT
The discovery of the physiological roles of nitric oxide has revolutionized the understanding of regulation of vascular tone, platelet adhesion and aggregation, and immune activation. Perhaps the most intriguing aspect of nitric oxide (NO) is that it is a gas that, in the absence of receptors, can regulate both normal physiological events and mediate cytotoxicity under pathological conditions. NO is produced from L-arginine by NO synthases (NOS), yielding L-citrulline and NO. The regulation of L-arginine pathway activity occurs at the level of NO production. The metabolic syndrome is a cluster of insulin resistance, elevated blood pressure, and atherogenic dyslipidemia, a common basis of cardiovascular disease. It occurs in genetically susceptible individuals with environmental influences and has serious economic and social consequences. Pharmacological and non-pharmacological therapies should be individualized and targeted to normalize its alterations of blood pressure, HDL cholesterol, triglycerides and glucose values. Despite the increasing prevalence of the metabolic syndrome in the last decades, there has been little progress in the understanding of the precise mechanisms involved in the pathogenesis of this syndrome and its complications. Emerging evidence is available that NO, inflammation and oxidative stress play important roles in the physiopathology of this syndrome. This review summarizes and evaluates the participation of the L-arginine-NO pathway and oxidative stress in the physiopathology of the metabolic syndrome and cardiovascular events at the systemic level, as well as the effects of exercise on this syndrome.

No MeSH data available.


Related in: MedlinePlus