Abstract TP320: Endothelial Nitric Oxide Synthase (eNOS) Inhibition Abolishes the Exercise-Induced Improvement in Neurovascular and Neurobehavioral Stroke Outcomes

Abstract

Background: Clinically, it was shown that increased physical activity reduces the risk of stroke and severity of outcomes. However, the underlying mechanism is not clear. Endothelial nitric oxide synthase (eNOS) activation was shown to improve vascular function and reduce the risk of cardiovascular diseases. However, the role of eNOS in mediating short term exercise-induced improvement in stroke outcome was not previously studied. Accordingly, we tested the hypothesis that acute short term pre-stroke exercise improves stroke outcomes through increased eNOS activity, and that eNOS inhibition abolishes these beneficial effects. Methods: Male Wistar rats (300 g) were subjected to high intensity interval training (HIIT) through treadmill running sessions for four days (25 minutes/day), break for 2 days and then one acute bout for 30 minutes. Exercised animals were subjected to thromboembolic stroke at 1h, 6h, 24h or 72h after the last exercise session. At 24h after stroke, sedentary and exercised rats were tested for neurological outcomes, infarct size and cerebral edema. Western Blotting was used to measure the expression of active eNOS (p-S1177-eNOS) in brain and cerebral vessels. Additional control and 1h exercise groups were treated with eNOS inhibitor (L-NIO (L-N 5 -1-Iminoethyl ornithine)) right after stroke (I.P. injection, dose: 20 mg/Kg). Results: Acute exercise significantly reduced infarct size, edema and improved functional outcomes, and increased the expression of peNOS in the brain and cerebral vessels. eNOS inhibition significantly increased the infarct size, edema and worsened the neurobehavioral outcomes in exercised animals compared to non-treated group (table). Conclusion: Short term acute pre-stroke exercise significantly reduced neurovascular injury and improved neurobehavioral and functional outcomes after stroke, and eNOS inhibition abolished these beneficial effects.