Beneficial effects and mechanisms of long-term voluntary exercise on stroke events in stroke-prone spontaneously hypertensive rats

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Epidemiological studies have showed that physical exercise reduced the risk of cardiovascular disease, but the mechanisms are not clear. This study planned to examine how a long-term and moderate exercise affected on the stroke events caused by vascular endothelial dysfunction in stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP at pre-hypertensive stave were allowed to run voluntarily in a wheel for 8 wks (EX). Sedentary rats were placed in the cage without running (SE).EX rats decreased only slightly systolic blood pressure compared with SE, and reduced the incidence of stroke and mortality. In aortas of EX, phosphorylated Akt and endothelial nitric oxide synthase (eNOS) levels, eNOS activity and NO production were elevated compared with those SE. Whereas, expression of Nox1 and Nox4, NADPH oxidase components, the activity and superoxide production were lower in aortas of EX than SE. EX rats showed lower serum levels of inflammatory cytokines and chemokines. Furthermore, arterial thickening and collagen contents was attenuated in EX than SE.In aortas of EX, the phosphorylation of MAPKs, ERK1/2, JNK and p38 MAPK, and activating transcription factors of AP-1 and NF-kB were decreased. EX weakened macrophage infiltration and NF-kB-triggered inflammatory responses in cerebral lesion compared with SE. In conclusion, the beneficial training effect is closely related to increase in Akt-dependent eNOS activation and decrease in oxidative stress, and then mitigate the inflammation associated with hypertension in the vessels and ischemic changes in the brain even in genetic hypertensive animals with stroke risk.