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Smooth Muscle Cells Specific Mineralocorticoid Deletion Does Not Alter Middle Cerebral Artery Structure in Mice
Author(s) -
Pires Paulo Wagner,
McCurley Amy,
Jaffe Iris Zamir,
Dorrance Anne McLaren
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.685.25
Subject(s) - myograph , middle cerebral artery , lumen (anatomy) , anatomy , endocrinology , medicine , ischemia , biology , pathology , chemistry , artery
We demonstrated that remodeling of the middle cerebral artery (MCA) in rats is in part dependent on the mineralocorticoid receptor (MR). MR mediated MCA remodeling leads to reduction in lumen diameter and increase in wall thickness. These changes can increase stroke risk and damage after cerebral ischemia. Recent studies demonstrate that MR in smooth muscle cells (SMC) directly regulates gene expression and function. We hypothesized that MR deletion in SMC play a role in MCA remodeling. SMC‐specific MR deletion (SMC‐MR−/−, n=8) in mice was achieved through expression of CRE‐recombinase driven by a SMC‐specific promoter and loxP sequences flanking exons 4 and 5 of the MR gene. MR floxed, Cre negative (WT, n=7) littermates were controls. MCAs from 9 months‐old mice were mounted on a pressure myograph to assess passive structure. Data are mean ± SEM, SMC‐MR−/− vs WT, at 80mmHg intralumenal pressure. SMC‐MR−/− did not alter MCA lumen diameter (151.6±2.8 vs 155.7±2.6μm), outer diameter (169.1±2.8 vs 171.7±2.8μm), wall thickness (8.75±0.2 vs 8.0±0.3μm) and the wall‐to‐lumen ratio (0.06±0.01 vs 0.05±0.01). MR deletion did not alter extracellular parameters in the MCA, such as stress (696±24 vs 785.8±33), stiffness (β‐coefficient: 5.58±0.4 vs 5.56±0.3), and distensibility (68.4±5.6 vs 71.5±5.2). This data suggest that under normal physiological conditions SMC‐MR does not have deleterious effects in the MCA in mice.