title: Oxidative stress in the cardiorenal metabolic syndrome.
abstract: Excess visceral adiposity contributes to inappropriate activation of the renin-angiotensin-aldosterone system despite a state of volume expansion and of salt retention that contributes to subclinical elevations of pro-oxidant mechanisms. These adverse effects are mediated by excess generation of reactive oxygen species (ROS) and diminished antioxidant defense mechanisms. Excess tissue (i.e., skeletal muscle, liver, heart) free oxygen radicals contribute to impairments in the insulin-dependent metabolic signaling pathways that regulate glucose utilization/disposal and systemic insulin sensitivity. The generation of ROS is required for normal cell signaling and physiological responses. It is a loss of redox homeostasis that results in a proinflammatory/profibrotic milieu that promotes impairments in insulin metabolic signaling, reduced endothelial-mediated vasorelaxation, and associated cardiovascular and renal structural and functional abnormalities. These maladaptive processes are increasingly recognized as important in the progression of hypertension in the cardiorenal metabolic phenotype. There is increasing evidence to support a critical role for Ang II signaling through the AT(1)R and aldosterone actions through the MR in conjunction with an altered redox-mediating impaired endothelial, cardiac and renal function in this metabolic phenotype. There are emerging clinical data that indicate that therapies that target the renin angiotensin-aldosterone system (RAAS) also attenuate oxidative stress, and improve endothelial, cardiac and renal functions, which collectively contribute to reductions in hypertension.
authors.affiliation: Diabetes and Cardiovascular Center, Harry S Truman VA Medical Center and the University of Missouri-Columbia School of Medicine, Columbia, MO 65213, USA. whaleyconnella@health.missouri.edu
authors.forename: Adam
authors.initials: A
authors.lastname: Whaley-Connell
authors.forename: James R
authors.initials: JR
authors.lastname: Sowers
mesh_terms: D001794:Blood Pressure; D059347:Cardio-Renal Syndrome / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D006973:Hypertension / Q000209:etiology* / Q000473:pathology; D007333:Insulin Resistance; D019255:NADPH Oxidases; D009765:Obesity / Q000150:complications* / Q000473:pathology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D012084:Renin-Angiotensin System; D012307:Risk Factors
chemical_list: D017382:Reactive Oxygen Species; D019255:NADPH Oxidases