NAD(P)H oxidase-derived reactive oxygen species contribute to age-related impairments of endothelium-dependent dilation in rat soleus feed arteries

• Published in: Journal of applied physiology (1985) Vol. 110; no. 5; pp. 1171 - 1180
• Main Authors: TROTT, Daniel W, SEAWRIGHT, John W, LUTTRELL, Meredith J, WOODMAN, Christopher R
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Physiological Society 01.05.2011
• Subjects: Aging - physiology; Animals; Arteries - metabolism; Biological and medical sciences; Blood Flow Velocity - physiology; Endothelium, Vascular - physiology; Fundamental and applied biological sciences. Psychology; Hydrogen peroxide; Male; Muscle, Skeletal - blood supply; Muscle, Skeletal - physiology; NADPH Oxidases - metabolism; Oxidation; Oxygen; Proteins; Rats; Rats, Inbred F344; Reactive Oxygen Species - metabolism; Rodents; Vasodilation - physiology; Veins & arteries; Reactive oxygen species; Hydrogen peroxide; Rat; Enzyme; Rodentia; Superoxide dismutase; Artery; endothelium-derived hyperpolarizing factor; Endothelium; NAD; Vertebrata; Mammalia; Blood vessel; Circulatory system; Oxidoreductases; superoxide; Age; catalase
• DOI: 10.1152/japplphysiol.01037.2010
• ISSN: 8750-7587

We tested the hypothesis that age-related endothelial dysfunction in rat soleus muscle feed arteries (SFA) is mediated in part by NAD(P)H oxidase-derived reactive oxygen species (ROS). SFA from young (4 mo) and old (24 mo) Fischer 344 rats were isolated and cannulated for examination of vasodilator responses to flow and acetylcholine (ACh) in the absence or presence of a superoxide anion (O(2)(-)) scavenger (Tempol; 100 μM) or an NAD(P)H oxidase inhibitor (apocynin; 100 μM). In the absence of inhibitors, flow- and ACh-induced dilations were attenuated in SFA from old rats compared with young rats. Tempol and apocynin improved flow- and ACh-induced dilation in SFA from old rats. In SFA from young rats, Tempol and apocynin had no effect on flow-induced dilation, and apocynin attenuated ACh-induced dilation. To determine the role of hydrogen peroxide (H(2)O(2)), dilator responses were assessed in the absence and presence of catalase (100 U/ml) or PEG-catalase (200 U/ml). Neither H(2)O(2) scavenger altered flow-induced dilation, whereas both H(2)O(2) scavengers blunted ACh-induced dilation in SFA from young rats. In old SFA, catalase improved flow-induced dilation whereas PEG-catalase improved ACh-induced dilation. Compared with young SFA, in response to exogenous H(2)O(2) and NADPH, old rats exhibited blunted dilation and constriction, respectively. Immunoblot analysis revealed that the NAD(P)H oxidase subunit gp91phox protein content was greater in old SFA compared with young. These results suggest that NAD(P)H oxidase-derived reactive oxygen species contribute to impaired endothelium-dependent dilation in old SFA.