Hemodynamic Forces-Induced Biochemical Changes in Aortic wall: Effect on Redox State of the Tissue

Abstract

Shear stress and hydrostatic pressure-induced stretch are known to enhance the production of free radicals, causing oxidative stress in the vascular wall and have been implicated in endothelial inflammation and vascular lesions. Production of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and catalase probably constitute a key factor in maintaining the redox state of arterial wall in response to hemodynamic forces. In the present study, redox state of arterial wall at constant pulsatile/laminar shear and varying hydrostatic pressure (70 and 150 cm water) was evaluated. The aim was to study the pressure, in combination with different flow patterns (laminar/pulsatile shear stress), induced oxidative stress which presumably cause arterial wall inflammation leading to vascular legions. The level of reduced glutathione (GSH), lipid peroxidation (LPO) and enzymes known to contribute to the redox status of the cell/tissue, have been measured. Present study quantitatively evaluates the hemodynamic forces induced vascular oxidative stress. We individually assessed the activity of Superoxide Dismutase (SOD), catalase, glutathione peroxidase (GPx), xanthine oxidase (XO), and glutathione-s-transferase (GST) under hemodynamic stress. Secondary antioxidant enzymes like glucose-6-phosphate dehydrogenase (G6PD) and glutathione reductase (GR) were also measured. The increased oxidative stress under pulsatile shear stress and high hydrostatic pressure potentially suggests that vascular inflammation is the key to understand initiation of vascular lesions. Higher concentrations of SOD in arterial wall ought to be considered since this explains arterial wall antioxidant defense in vascular pathologies, which potentially involve oxidative stress. In conclusion, pulsatile shear stress in combination with hydrostatic pressure is a weak inducer of antioxidant defense in blood vessels, hence, considered to be atherogenic. The finding is relevant to both the normal and pathophysiologically relevant hemodynamically stress rabbit thoracic aorta.