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

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.

Plasmatic and Intracellular Markers of Oxidative Stress in Normal Weight and Obese Patients with Polycystic Ovary Syndrome

“…The scenario concerning OS and metabolic syndrome (MS) is complex and several studies reported the role of OS in the development of MS [26,27]. In the context of a genetic predisposition to IR induced by excessive caloric intake or sedentary lifestyle, it has been hypothesized a diet-induced OS [28].…”

Beneficial effects of melatonin on serum nitric oxide, homocysteine, and ADMA levels in fructose-fed rats

“…The production of O À 2 may contribute to the oxidative inactivation of endotheliumderived NO, by converting it to ONOO À . ONOO À and notably its conjugated peroxynitrous acid are highly unstable in aqueous phase, and they isomerize and decompose to nitrate and nitrite (Assumpçao et al, 2008;Bestermann, 2011;Dayal & Lentz, 2005;Dayal et al, 2004). With regard to these data, endothelium-dependent vasodilatation might be decreased due to decreased bioavailability of NO and levels of NO metabolites might be raised due to oxidative stress.…”

“…There is now evidence that insulin modulates the expression of endothelial nitric oxide synthase (eNOS) and stimulates nitric oxide (NO) production, causing vasodilation. On one hand, in the state of insulin resistance, the effects of insulin on eNOS and NO become blunted, resulting endothelial dysfunction (Assumpçao et al, 2008;Johnson et al, 2007;Marchesi et al, 2009). On the other hand, blood homocysteine (Hcy) and asymmetric dimethylarginine (ADMA) levels are markers of endothelial damage and subsequent cardiovascular disorders, and these parameters are linked to other metabolic syndrome symptoms (Bestermann, 2011).…”

Dysregulated relationship of inflammation and oxidative stress in major depression

“…Chronic inflammation and oxidative stress have been implicated in the pathophysiology of Major Depressive Disorder (MDD) (Berk et al, 2011; Capuron and Miller, 2011; Chauhan and Chauhan, 2006; Croonenberghs et al, 2002; Forlenza et al, 2007; Khanzode et al., 2003; Maes, 2011a,b, 1999; Miller, 2010; Raison and Miller, 2011; Wolkowitz et al, 2008) as well as a number of serious medical conditions (Maes et al, 2011b), including cardiovascular disease and atherosclerosis (Krishnan, 2010; Lakshmi et al, 2009; Tousoulis et al, 2008; Uno and Nicholls, 2010), chronic renal disease (Cottone et al, 2008), pulmonary disease (Jelic and Le Jemtel, 2008), rheumatoid arthritis (Stamp et al, 2012), certain cancers (Khansari et al, 2009; Maes et al, 2011b; Reuter et al, 2010), metabolic syndrome, obesity and diabetes (Agrawal et al, 2007; Assumpcao et al, 2008; Ferder et al, 2006; Guerrero-Romero and Rodriguez-Moran, 2006), and in the normal physiology of cellular aging and immuno-senescence (Cannizzo et al, 2011; De la Fuente and Miquel, 2009). While inflammation and oxidation have generally been studied separately in these conditions, the interplay between them has been less well-studied, despite mounting evidence that their interaction plays a major role in the pathogenesis of many diseases (Ambade and Mandrekar, 2012; Forlenza and Miller, 2006; Maes et al, 2011e, 2007; Rahman, 2003; Sarandol et al., 2007a).…”