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ACE2 Deficiency Augments Cerebrovascular Dysfunction during Aging
Author(s) -
Peña-Silva Ricardo Alfonso,
Chu Yi,
Mitchell Ian J,
Miller Jordan D,
Penninger Josef M,
Faraci Frank M,
Heistad Donald D
Publication year - 2012
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.26.1_supplement.lb651
Subject(s) - medicine , oxidative stress , endocrinology , endothelial dysfunction , nitrotyrosine , angiotensin ii , cerebral arteries , knockout mouse , nadph oxidase , vasomotor , vasodilation , nitric oxide , nitric oxide synthase , blood pressure , receptor
Angiotensin II produces oxidative stress and endothelial dysfunction. ACE2 converts angiotensin II to angiotensin 1–7 and may protect against effects of angiotensin II. We tested the hypothesis that ACE2 deficiency increases oxidative stress and vasomotor dysfunction in cerebral arteries, and examined the role of ACE2 in vascular aging. ACE2 was present at relatively low levels in cerebral arteries. Systolic arterial pressure was similar in adult and old ACE2 knockout (KO) and wild‐type (WT) mice. Maximal dilatation to acetylcholine (ACh) was impaired in the basilar artery from adult ACE2 KO mice compared to adult WT. In old mice, maximal dilatation to ACh was impaired in WT mice but severely impaired in ACE2 KO mice (P<0.05). The antioxidant tempol (1 mM) improved responses to ACh in adult and old ACE2 KO and WT mice. Nitrotyrosine staining in the basilar artery was increased in adult ACE2 KO mice and in old ACE2 KO and WT mice. Expression of NAD(P)H oxidase subunits Nox2 and p47phox, and of pro‐inflammatory molecules Rcan1 and TNFα, was increased in cerebral arteries from old ACE2 KO and WT animals. In summary, ACE2 deficiency impaired vasomotor function in cerebral arteries from adult mice and augments endothelial dysfunction during aging. Oxidative stress plays a critical role in cerebrovascular dysfunction induced by ACE2 deficiency and aging. NIH grants NS‐24621, HL‐38091, HL‐62984; AHA 0815525G, 10PRE3780044.