Targeting ER Stress in Vascular Dysfunction
“Targeting ER Stress in Vascular Dysfunction”
Aging and obesity are both risk factors for cardiovascular disease (CVD). One process that links both of these conditions to CVD is vascular dysfunction. Data from animal studies indicate that endoplasmic reticulum (ER) stress may play an important role in the development of endothelial dysfunction in aging and obesity. Therefore, the goal of this study is to investigate the relative contributions of aging and obesity on vascular dysfunction and ER stress. Additionally, this study will determine if taking an oral supplement for 8 weeks will improve vascular dysfunction and ER stress. Results from this study have the potential to identify a safe treatment option for improving vascular function in aging and obese populations.
Drug - Acetylcholine
Endothelium-dependent vasodilation will be determined via graded intra-arterial infusions of acetylcholine (ACh). Doses of 1, 4, 8, and 16 Î¼g/100ml forearm volume/min will be infused in the brachial artery for 3 minutes each.
Drug - Sodium Nitroprusside
Endothelium-independent vasodilation will be determined via graded intra-arterial infusions of sodium nitroprusside (SNP). Doses of 0.25, 0.5, 1, and 2 Î¼g/100ml forearm volume/min will be infused in the brachial artery for 3 minutes each.
Drug - Ascorbic Acid
The influence of oxidative stress on arterial stiffness and vasodilation will be assessed by using intravenous ascorbic acid (AA). A single supra-physiological dose of 0.06 g/kg fat-free mass (FFM) will be infused over 20 min followed by a drip infusion of 0.02 g/kg FFM administered over 60 min.
Targeting Endoplasmic Reticulum Stress in Aging- and Obesity-Induced Vascular Dysfunction