Postnatal exposure to voluntary exercise but not the antioxidant catechin protects the vasculature after a switch to an atherogenic environment in middle-age mice

Abstract

We aimed to evaluate the lasting functional imprinting of exercise (EX) and catechin (CAT) on the vascular function of middle-age mice switched to a proatherogenic environment. C57BL/6J mice (n=10-15 in each group) fed a regular diet (RD) were exposed from the age of 1 to 9 months either to EX (voluntary running; 2.7± 0.2 km/day), to the polyphenol CAT (30 mg/kg/day in drinking water), or to physical inactivity (PI). At 9 months of age, EX and CAT were stopped and mice either remained on the RD or were fed a Western diet (WD) for an additional 3 months. At 12 months of age, mice from all groups fed a WD had similar body mass, systolic blood pressure, and plasma total cholesterol, glucose, insulin, and isoprostane. Compared to the RD, the WD induced an indomethacin-sensitive aortic endothelium-dependent and independent dysfunction in PI mice (p<0.05) that was prevented by both EX and CAT; this benefit was associated with a higher (p< 0.05) non-nitric oxide/non-prostacyclin endothelium-dependent relaxation. While EX, but not PI or CAT, prevented vascular dysfunction induced by the WD in cerebral arteries, it had no effect in femoral arteries. The profiles of activity of antioxidant enzymes and of proinflammatory gene expression in the aorta suggest a better adaptation of EX>CAT>PI mice to stress. In conclusion, our data suggest that a postnatal exposure to EX, but not to CAT, imprints an adaptive defense capacity in the vasculature against a deleterious change in lifestyle.Correspondence to: Eric Thorin.eric.thorin@umontreal.ca. Electronic supplementary material The online version of this article

Endothelium-dependent control of cerebrovascular functions through age: exercise for healthy cerebrovascular aging

“…1): a decline in resting heart rate after one year of exercise training (82), a higher expression of antioxidant defenses (83), and a reduced inflammation in combination with increased NO release (70,97,195), as well as an increased production of endothelial progenitor cells (135). These data demonstrate that the vascular endothelium is highly sensitive to exercise as we recently reported in mice (139). Besides stimulating the endothelium of the cerebral arteries, chronic physical training is also a good "neuronal exercise" leading to remarkable changes in brain function and neuronal adaptations that have been very well reviewed by Mattson (161).…”

“…Acutely, however, a change in flow rate will stimulate the release of vasoactive factors modifying arterial diameter within seconds to normalize shear stress (72). Both endothelium-dependent dilations (30,64,85,139) and endothelium-independent constriction (40,146,217,227) or both (84,170,213) have been reported in isolated cerebral arteries exposed to changes in shear stress. Endothelium-dependent flow-mediated dilation (FMD) is consistently described in peripheral arteries (123,130,198).…”

“…Therefore, do the transitory increases in shear stress during exercise preserve the endothelial function globally? We demonstrated in healthy mice that ran on a voluntary basis from the age of 1 to 9 mo, that FMD in the isolated posterior cerebral artery was better compared with physically inactive animals (139). Because the posterior cerebral artery feeds the cerebellum in mammals, an area where CBF increases during exercise (Table 1), it could be speculated that shear stress is one of the positive effector that maintains endothelial function.…”

“…It is no longer questionable that physical inactivity is a cause of chronic diseases in general such as type-2 diabetes, coronary artery disease, and cancer (31), but how the aerobic exercise capacity can maintain cerebrovascular health remains an important biological question. The vascular endothelium is stimulated by high shear stress in culture (60,80), while we observed that lifelong voluntary exercise in mice, which likely induces repeated and acute increases in shear stress, contributes to the maintenance of flow-mediated, endothelium-dependent dilation in isolated cerebral arteries (139). It is therefore possible that the beneficial effects of exercise on cerebrovascular function through age are partly dependent on its beneficial impact on the endothelium.…”

“…Cerebral vascular aging is a natural process consequent of the gradual decline in the function of the cerebrovascular endothelial cells (ECs) (63,69,139), the "cells that rule them all" (69). Second, aging is characterized by the stiffening of the carotid arteries (92), transmitting the pulsations of peripheral flow to the brain microcirculation and thus favoring pulse wave encephalopathy (179).…”