Reversing the effects of chronic stress on the aorta with exercise training

Abstract

Individuals with increased levels of chronic stress have an increased aortic stiffness which is a strong, independent risk factor for cardiovascular disease. Additionally, chronic stress is associated with a decreased capacity for endothelium‐dependent, nitric oxide (NO)‐induced vasorelaxation which may contribute to the aortic stiffness and increased after load on the heart. Using the unpredictable chronic mild stress protocol (UCMS), lean zucker rats (LZR; healthy rats) develop impaired vascular reactivity in aortic rings concomitant to the onset of chronic stress pathologies. Therapeutic interventions aimed at improving endothelial functioning are therefore considered important avenues for improving CV outcomes in stressed patients. We hypothesized that a chronic aerobic exercise intervention would improve endothelium‐dependent relaxation to methacholine in isolated aortic rings of stressed LZRs. A total of 22 LZRs underwent 8 weeks of a treadmill exercise protocol beginning at 9 weeks of age. The animals were separated into 4 groups: sedentary LZR (LZR; n=7); UCMS LZR (UCMS‐LZR; n=8); exercise and UCMS (ExUCMS‐LZR n=7). Following the intervention, the thoracic aorta was dissected out from each animal and sectioned into rings, some of which were then mounted into an ex vivo wire tension myograph system. The remaining rings were evaluated for NO production in a DAF‐FM diacetate assay. Force transduction was used to measure the changes in aortic tension in response to pharmacological agonists. The aortic rings were mechanically set to 1 gram of tension then pre‐constricted using phenylephrine (1×10‐6μM), followed by a gradual dilation induced by increasing concentrations of methacholine (1×10‐9, 1×10‐8, 1×10‐7, 1×106, 1×10‐5 μM respectively). The LZR group demonstrated greater methacholine‐induced maximal vasorelaxation compared to the UCMS‐LZR group (83% vs. 78%). The ExUCMS‐LZR group experienced the greatest maximal dilation (90%) as well as increased values of NO production measured in the DAF assay compared to LZR group and UCMS‐LZR group. These results demonstrate that 8 weeks of aerobic exercise enhances endothelial bioavailability and/or production of NO which improves endothelium‐dependent vasorelaxation in the aortas of stressed LZRs even more so than the sedentary control. Exercise training may therefore be an important therapy for promoting greater arterial compliance of chronically stressed individuals.Support or Funding InformationNIHAHA