Nitrite supplementation reverses vascular endothelial dysfunction and large elastic artery stiffness with aging.

摘要: Cardiovascular diseases (CVD) remain the leading cause of death in modern societies (Lloyd-Jones et al.). Advancing age is major risk factor for CVD (Lakatta 2002; Lakatta & Levy 2003). Most are linked to disorders arteries al.) and it now recognized that aging increases large part by causing arterial dysfunction, which then leads clinical vascular cardiac 2003). Many changes likely contribute increased with aging. One these development endothelial as most commonly indicated impaired endothelium-dependent dilation (EDD) (Celermajer al. 1994; Taddei 1995; Impaired EDD mediated excessive superoxide, at least a result oxidant enzyme nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase) (Zalba 2000; Bedard Krause 2007; Donato Durrant 2009). Increased superoxide reduces bioavailability nitric oxide (NO) both reacting NO form peroxynitrite oxidizing tetrahydrobiopterin (BH4), an essential co-factor production synthase (eNOS) (Cosentino 1998; 2001; Landmesser 2003; Blackwell 2004; Shi 2004). Another key change stiffening elastic 2003), possibly dysfunction (Fitch Wilkinson Large artery stiffness has emerged independent age-associated therapeutic target Nilsson 2009; Mitchell al.; Vlachopoulos 2010). Oxidative stress inflammation believed be important mechanisms contributing effects on (Brandes 2005; Csiszar 2008; Ungvari 2010). Arterial oxidative develops consequence NADPH oxidase or other (eNOS uncoupling, mitochondrial dysfunction) (Vasquez-Vivar Rippe 2010) via selective reductions antioxidant enzymes, including dismutase (SOD) (Sun As stress, injury causes, also aging, expression pro-inflammatory cytokines such interleukins 1 6 (IL-1, IL6), interferon γ (INFγ) tumor necrosis α (TNFα) (Csiszar 2010; 2010). Given above, treatments improve reverse middle/older may prevent much increase Lonn Seals In this context, nitrite anion (inorganic nitrite) would seem hold promise. Once considered inert byproduct metabolism, physiologically storage (Lundberg Weitzberg 2008). Nitrite cytoprotective molecule have broad potential prevention treatment (Calvert Lefer; Lundberg Sodium administration protects against ischemia/reperfusion (Bryan Bryan Gonzalez 2008) improves hypercholesterolemic mice (Stokes However, efficacy sodium treating entirely unknown. In present study, we hypothesized short-term oral old while having no young mice. secondary aim, sought gain initial insight into nitrite-induced improvements function might mediated, particularly those related reduced inflammation.