Shear stress induces eNOS mRNA expression and improves endothelium-dependent dilation in senescent soleus muscle feed arteries

Abstract

We tested the hypothesis that increased intraluminal shear stress induces endothelial nitric oxide (NO) synthase (eNOS) mRNA expression and improves endothelium-dependent dilation in senescent soleus muscle feed arteries (SFA) by increasing NO production. SFA were isolated from young (4 mo) and old (24 mo) male Fischer 344 rats and cannulated with two resistance-matched glass micropipettes. SFA were exposed to no flow (NF), low flow (LF), intermediate flow (IF), or high flow (HF) for 4 h. Mean intraluminal shear stress ranged from 0 to 82 dyn/cm(2). At the end of the 4-h treatment period, eNOS mRNA expression was assessed in each SFA. eNOS mRNA expression was significantly lower in old NF SFA than in young NF SFA. In old SFA, eNOS mRNA expression was induced by IF (+154%) and HF (+136%), resulting in a level of expression that was not different from that of young SFA. In a separate series of experiments, SFA were pretreated with NF or HF for 4 h, and endothelial function was assessed by examining vasodilator responses to ACh. ACh-induced dilation was less in old NF SFA than young NF SFA. Pretreatment with HF improved ACh-induced dilation in old SFA such that the response was similar to that of young SFA. In the presence of N(omega)-nitro-L-arginine to inhibit NOS, ACh-induced dilation was inhibited in old HF SFA such that the response was no longer greater than that of old NF SFA. These results indicate that increased intraluminal shear stress induces eNOS mRNA expression and improves endothelium-dependent dilation in senescent SFA by increasing NO production.

Vascular Adaptation to Exercise in Humans: Role of Hemodynamic Stimuli

“…Indeed, low The role of shear stress patterns in modulating vascular health is also supported by studies in isolated and pressurized arteries. For example, isolated rat soleus feed arteries exposed to high flow and shear stress for 4 hrs exhibited increased expression of eNOS mRNA and enhanced endothelium-dependent dilation (321). Conversely, exposure of rat carotid arteries…”

Physical Activity in the Prevention and Treatment of Coronary Artery Disease

“…An increase in shear stress (eg, during physical activity) has been proved to enhance eNOS mRNA and protein expression and promote phosphorylation of the serine 1177 residue of the enzyme, thereby boosting vascular NO production 31, 32, 33, 34. However, animal studies suggest that after a few months of exercise training, eNOS expression levels reduce to the preexercise state 35.…”

Shear Stress Mediates Endothelial Adaptations to Exercise Training in Humans

“…14,15 Indeed, increases in intraluminal shear stress improve NO-mediated endothelium-dependent dilation in animals. 16,17 However, to our knowledge, this has not been directly addressed experimentally in humans.…”