Age‐Related Alterations in Reactivity of Cerebral Arterioles: Role of Oxidative Stress

Abstract

Aging impairs eNOS-dependent reactivity of cerebral arterioles via an increase in superoxide produced by activation of NAD(P)H oxidase.

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

“…Although we cannot compare absolute differences in the amount of superoxide production between arteries due (Miller et al 2005(Miller et al , 2009. Similar to previous studies, we find that scavenging superoxide improves EDD in conduit and cerebral arteries from old mice (Blackwell et al 2004;Lesniewski et al 2009;Mayhan et al 2008;Modrick et al 2009) and does not affect EDD in conduit arteries from young or old CR mice (Csiszar et al 2009). However, we demonstrate that scavenging superoxide in the MCA from young and old CR mice results in reduced EDD, which is in accordance with previous studies demonstrating reactive oxygen species contribute to the dilation of resistance arteries in skeletal muscle (Sindler et al 2013;Trott et al 2011), cardiac muscle (Miura et al 2003;Feng et al 2010;Kang et al 2011), and cerebral tissue (Drouin et al 2007).…”

“…Cerebral arteries have greater NADPH oxidase activity compared with conduit arteries and this contributes to their greater production of superoxide (Miller et al 2005(Miller et al , 2009. Aging leads to increased NADPH oxidase expression in cerebral arteries (Mayhan et al 2008) as well as increased NADPH oxidase expression and activity in the aorta Rippe et al 2010). Inhibiting NADPH oxidase activity with apocynin led to improved EDD in the MCAs of old AL mice, in agreement with our previous findings in carotid arteries Rippe et al 2010), inhibiting NADPH oxidase does not affect EDD in the carotid arteries of old CR mice.…”

Role of oxidative stress and AT1 receptors in cerebral vascular dysfunction with aging

“…Aging is associated with diverse vascular changes (4,10,17,20,21,28,29,34). For example, resting cerebral blood flow (10), endothelial function (10,21,29,34), neurovascular coupling (34,38), and vascular responses to hypercapnia all decrease with aging (10, 34). Despite the enormous potential impact of these changes, few studies have attempted to define the mechanisms that produce cerebral vascular dysfunction with aging.…”

“…In the cerebral circulation, for example, aging produces both structural and functional changes (10,20,21,29,34). Aging has an enormous negative impact on cerebral blood vessels and is the major risk factor for cerebral vascular disease, stroke, Alzheimer's disease, and vascular cognitive impairment (19,36).…”

The impact of aging on spreading depolarization in the intact and ischemic rat brain

“…Ischemia itself imposes considerable extracellular K + accumulation above the dilation and/or constriction threshold (20 mM) 66 , and NO is quickly eliminated by its reaction with superoxide yielding peroxynitrite 69 . Limited NO availability due to increased free radical production causes dysfunctional NO-based vasodilation during physiological aging, as well 70,71 . Ischemia superimposed on aging, therefore, is thought to potentiate the impairment of NO-based vasoregulation in the face of high [K + ] e , which may lead to a higher incidence of inverse neurovascular coupling in the aged ischemic brain.…”