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Flow‐Mediated, Redox‐Dependent AT1R Regulation Determines Collateral Growth Capacity
Author(s) -
Unthank Joseph L.,
Miller Steven J.,
Labarrere Carlos A.
Publication year - 2010
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.24.1_supplement.978.14
Subject(s) - downregulation and upregulation , losartan , endocrinology , medicine , angiotensin ii , captopril , oxidative stress , immunostaining , chemistry , p22phox , nadph oxidase , receptor , blood pressure , immunohistochemistry , biochemistry , gene
We previously observed flow‐related suppression of AT1R mRNA in collaterals of the SHR (Miller, 2008) which is characterized by oxidative stress, metabolic abnormalities and impaired collateral growth (CG). This study was undertaken to determine the role of flow‐related AT1R regulation in both the promotion of CG in normotensive WKY and CG impairment in SHR. RT‐PCR demonstrated upregulation (3.0±0.7X) in WKY but suppression in SHR (−2.4±0.5X). Immunostaining for AT1R demonstrated significant upregulation throughout the arterial wall in WKY but not SHR collaterals (see table). Losartan prevented CG and the associated endothelial proliferation in WKY. Captopril but not losartan restored CG in SHR and prevented AT1R down‐regulation. Captopril also restored normal p22phox expression in SHR. We propose that AT1R upregulation and stretch‐dependent AT1R activation is induced by elevated shear stress in WKY but prevented by oxidative stress in SHR. Number of cells in each wall layer with significant immunoreactivity, as percent of total cells. A remarkable increase is observed in all wall layers of the WKY collateral.% Cells with AT1R ImmunoreactivityIntima Media AdventitiaWKY‐Control 8±2.0 10±2.1 10±1.2 WKY‐Collateral 45±5.6 * 74±8.2 * 43±8.2 * SHR‐Control 6±0.6 9±1.1 11±2.1 SHR‐Collateral 3±0.4 9±1.8 3±2.6 *N=3* p≤0.05.Supported by HL42898.