Mechanical Signals Promoting Healthy Vascular Endothelial and Smooth Muscle Cell Function in Aged Arteries

Abstract

Peripheral arterial function is impaired with age, increasing the risk of cardiovascular disease. One therapeutic modality for improving arterial function in aged arteries is aerobic exercise; however, the signals associated with exercise that lead to improved arterial function are not fully understood. The aim of the research in this dissertation is to determine the importance of hemodynamic changes associated with aerobic exercise (increased intraluminal pressure and shear stress) which may serve as mechanical signals to promote healthy vascular endothelial and smooth muscle function in aged arteries. We hypothesized that a short-duration increase in intraluminal pressure would: 1) improve nitric oxide (NO)-mediated endothelium-dependent dilation in aged soleus muscle feed arteries (SFA); 2) improve vasoconstrictor responses in aged SFA via the Rho pathway; 3) improve vascular smooth muscle contractility in aged denuded (endothelium removed) SFA through the Rho pathway; and, 4) in combination with increased shear stress, induce greater improvements of endothelium-dependent dilation than a short-duration increase in pressure alone. SFA from young (4 mo) and old (24 mo) Fischer 344 rats were isolated and cannulated. Intact SFA or denuded (endothelium removed) SFA were exposed to increased intraluminal pressure for 1 h before assessment of vasodilator or vasoconstrictor function. The results from these experiments demonstrated that exposure to a short-duration increase in pressure, within a range believed to be present in SFA during exercise 1) improved NO-mediated, endothelium-dependent vasodilator responses in aged SFA; 2) improved vasoconstrictor responses in aged intact SFA via the Rho pathway; 3) impaired vasoconstrictor responses in aged denuded SFA; and, 4) did not interact with increased shear stress to produce greater improvements in endothelium-dependent dilation than pressure alone. Collectively, these data indicate that a short-duration increase in intraluminal pressure improves age-impaired arterial function and suggests that increased intraluminal pressure is one mechanical signal associated with aerobic exercise which promotes healthy endothelial and smooth muscle function in aged arteries.