The blood pressure independent effect of exercise and salt on endothelial function
Date
2016
Authors
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Publisher
University of Delaware
Abstract
Excess salt intake has been shown to increase blood pressure (BP) and can ultimately lead to the development of subclinical diseases such as hypertension (HTN) and atherosclerosis, precursors to cardiovascular disease (CVD). High salt diets also contribute to the development of endothelial dysfunction in both human and rodent studies and is characterized by a reduction in endothelial-dependent dilation (EDD) independent of changes in BP. Endothelial dysfunction is considered a non-traditional risk factor for atherosclerosis and HTN. The beneficial effects of exercise on CVD have been well established in both humans and rodents. Several studies have examined the protective effects of exercise as a preventive strategy against various models of vascular dysfunction. Hence, the long-term goal of this project was to determine whether exercise could attenuate salt induced vascular dysfunction and aortic stiffness independent of BP changes. Our central hypothesis was that vascular function would be preserved in voluntary wheel running rats fed a high salt diet. Additionally, we hypothesize that voluntary wheel running would reduce oxidative stress, aortic stiffness and preserve NO in rats fed a high sodium diet.
In our first set of experiments, high salt (HS) fed rats had significantly impaired endothelial dependent relaxation (EDR; P<0.05) in the femoral artery when compared to the matched normal salt group (NS) independent of changes in BP. Exercise abolished losses in EDR (P <0.05) and augmented EDR in both dietary conditions. Furthermore, EDR was significantly (P<0.05) restored in the HS animals by the addition of endogenous antioxidants tempol and apocynin indicating the role of reactive oxygen species (ROS). Exogenous antioxidant SOD-2 was significantly upregulated (P<0.05) in the aortic tissue of the high salt exercise (HS-EX) group when compared to the sedentary groups and may be responsible for normalizing EDR in that group of animals. In addition, phosphorylated eNOS (eNOS-P) was increased (P<0.05) in the HS-EX group suggesting there may be an increase in eNOS activity as a result of exercise. Lastly, there was a loss of EDR (P<0.05) when the exercising animals were given tempol or apocynin. This suggests there may be a critical level of ROS needed to maintain endothelial function.
In our second set of studies, we were interested if exercise could protect the vasculature against increases in arterial stiffness as a result of a high salt diet. Once again HS fed animals failed to have a rise in BP as a result of their diet. Pulse wave velocity (PWV) was used as a measure of aortic stiffness. There was an increase in PWV over the course of six weeks in the HS group from baseline measurements (P<0.05). This change coincided with an increase in Collagen IA expression (P<0.05), indicating a salt induced increase in aortic stiffness. Both exercise groups had significantly lower PWV values (P<0.05) and aortic collagen protein expression (P<0.05) than the HS group. In addition, animals fed a HS diet had decreased aortic eNOS expression (P<0.05) that was not recovered with exercise. Exercise did however increase eNOS activity as evident by significantly higher aortic eNOS-P expression (P<0.05) in the HS-EX group. TGF-β expression was significantly higher in the aortas of the HS group (P<0.05) but not the HS-EX group. SOD-2 was significantly elevated in the aortas of the HS-EX compared to both sedentary groups (P<0.05). This upregulation may have been responsible for normalizing nitrotyrosine levels which were significantly elevated under HS sedentary conditions (P<0.05). These findings suggest that exercise can offset structural changes in the aortas of HS fed rats. Furthermore, it may do so by an up regulation of the endogenous antioxidant SOD-2.
In summary, exercise protected high salt fed rats from losses in endothelial function and increases in aortic stiffness. Impaired vascular function occurred in the presence of an increase in ROS and loss of NO production. Therefore, it appears that exercise has potential as a protective tool against a chronic high salt diet that has become a hallmark of American society.