Logo image
Back
Role of oxidative stress and AT1 receptors in cerebral vascular dysfunction with aging
Journal article   Open access   Peer reviewed

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

Mary L Modrick, Sean P Didion, Curt D Sigmund and Frank M Faraci
American journal of physiology. Heart and circulatory physiology, Vol.296(6), pp.H1914-1919
06/2009
DOI: 10.1152/ajpheart.00300.2009
PMCID: PMC2716103
PMID: 19395552
url
https://doi.org/10.1152/ajpheart.00300.2009View
Published (Version of record) Open Access

Abstract

Vascular dysfunction occurs with aging. We hypothesized that oxidative stress and ANG II [acting via ANG II type 1 (AT(1)) receptors] promotes cerebral vascular dysfunction with aging. We studied young (5-6 mo), old (17-19 mo), and very old (23 +/- 1 mo) mice. In basilar arteries in vitro, acetylcholine (an endothelium-dependent agonist) produced dilation in young wild-type mice that was reduced by approximately 60 and 90% (P < 0.05) in old and very old mice, respectively. Similar effects were seen using A23187, a second endothelium-dependent agonist. The vascular response to acetylcholine in very old mice was almost completely restored with tempol (a scavenger of superoxide) and partly restored by PJ34, an inhibitor of poly(ADP-ribose) polymerase (PARP). We used mice deficient in Mn-SOD (Mn-SOD(+/-)) to test whether this form of SOD protected during aging but found that age-induced endothelial dysfunction was not altered by Mn-SOD deficiency. Cerebral vascular responses were similar in young mice lacking AT(1) receptors (AT(1)(-/-)) and wild-type mice. Vascular responses to acetylcholine and A23187 were reduced by approximately 50% in old wild-type mice (P < 0.05) but were normal in old AT(1)-deficient mice. Thus, aging produces marked endothelial dysfunction in the cerebral artery that is mediated by ROS, may involve the activation of PARP, but was not enhanced by Mn-SOD deficiency. Our findings suggest a novel and fundamental role for ANG II and AT(1) receptors in age-induced vascular dysfunction.
 Basilar Artery - drug effects Superoxide Dismutase - genetics Reactive Oxygen Species - metabolism Vasodilator Agents - pharmacology Angiotensin II - metabolism Cerebrovascular Circulation - physiology Acetylcholine - pharmacology Cerebrovascular Circulation - drug effects Mice, Inbred C57BL Oxidative Stress - physiology Calcimycin - pharmacology Receptor, Angiotensin, Type 1 - genetics Animals Aging - physiology Mice, Mutant Strains Receptor, Angiotensin, Type 1 - metabolism Mice Basilar Artery - physiology Vasodilation - physiology Ionophores - pharmacology Superoxide Dismutase - metabolism

Details

Metrics

37 Record Views
86 Times Cited - Web of Science
Logo image