Beneficial effects of lifelong caloric restriction on endothelial function are greater in conduit arteries compared to cerebral resistance arteries

Endothelial dysfunction occurs in conduit and cerebral resistance arteries with advancing age. Lifelong caloric restriction (CR) can prevent the onset of age-related dysfunction in many tissues, but its effects on cerebral resistance artery function, as compared with conduit artery function, have not been determined. We measured endothelium-dependent dilation (EDD) in the carotid artery and middle cerebral artery (MCA) from young (5–7 months), old ad libitum fed (AL, 29–32 months), and old lifelong CR (CR, 40 % CR, 29–32 months) B6D2F1 mice. Compared with young, EDD for old AL was 24 % lower in the carotid and 47 % lower in the MCA (p 0.05), but was 25 % lower than young in the MCA (p 0.05), with no effect in young or old CR (p > 0.05). In the MCA, incubation with TEMPOL or the NADPH oxidase inhibitor apocynin augmented EDD in old AL (p < 0.05), but reduced EDD in young and old CR (p < 0.05). Thus, age-related endothelial dysfunction is prevented by lifelong CR completely in conduit arteries, but only partially in cerebral resistance arteries. These benefits of lifelong CR on EDD result from lower oxidative stress and greater NO bioavailability.