Smaller cerebrovascular arteries have a greater age‐related endothelial dysfunction and a blunted response to life‐long caloric restriction

Life‐long caloric restriction (CR) protects against age‐associated diseases, but its effect on cerebrovascular arteries of varying size is unknown. We measured ex vivo endothelium‐dependent dilation (EDD, response to acetylcholine [ACh]) of larger (carotid) and smaller (middle cerebral artery [MCA]) arteries from young (Y‐AL, 6 mo, n=12) and old (O‐AL, 29–31 mo, n=12) ad libitum fed and old CR (O‐CR, 29–31 mo, n=19, 40%0.05). TEMPOL (superoxide dismutase mimetic) restored carotid artery EDD in O‐AL (91±3%, P<0.05), but had no effect in Y‐AL and O‐CR (P>0.05). In the MCA, TEMPOL restored EDD partially in O‐AL (43±16%, P<0.05), but diminished ACh‐induced dilation in O‐CR and Y‐AL (P<0.05). Thus, smaller cerebrovascular arteries have a greater age‐related reduction in endothelial function. Life‐long CR preserves endothelial function with age in larger arteries, but this response is blunted in smaller cerebrovascular arteries. Supported by AG029337 , AG040297 , AG033196