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Role of Oxidative Stress and Angiotensin II in Cerebral Vascular Dysfunction with Aging
Author(s) -
Modrick Mary L.,
Didion Sean P.,
Sigmund Curt D.,
Faraci Frank M.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1151.21
Subject(s) - medicine , endocrinology , oxidative stress , endothelial dysfunction , acetylcholine , cerebral arteries , angiotensin ii , basilar artery , vasodilation , endothelium , aorta , receptor
Endothelial dysfunction occurs with aging. We hypothesized that oxidative stress and angiotensin II (Ang II, via AT1a receptors) promote cerebral vascular dysfunction with aging. We studied young (∼6 mo), old (∼17 mo) and very old (22–25 mo) mice. In basilar arteries, acetylcholine (an endothelium‐dependent agonist) produced dilation in young mice that was reduced by ∼60 and 90% (P<0.05) in old and very old wild‐type mice, respectively. Similar changes were seen in arteries from mice deficient in Mn‐superoxide dismutase (MnSOD +/−). Relaxation of aorta and carotid artery to acetylcholine was normal in old mice and only modestly affected in very old mice. The cerebral vascular ressponse to acetylcholine in very old mice was largely (∼80%) restored with Tempol (a scavenger of superoxide) and partly (∼40%) restored by PJ34, an inhibitor of PARP. Cerebral vascular responses were similar in young mice lacking AT1a receptors and wild‐type mice. Responses of basilar arteries to acetylcholine were reduced by >50% in old AT1a wild‐type (P<0.05). In contrast, vasodilation to acetylcholine was normal in old AT1a deficient mice. Thus, age‐related endothelial dysfunction occurred earlier and to a greater extent in basilar arteries compared to non‐cerebral blood vessels, but was not enhanced by MnSOD deficiency. Our findings suggest a novel role for Ang II in age‐related cerebral vascular dysfunction.