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Regulation of mineralocorticoid receptor expression by hypoxia and ischemia. (853.6)
Author(s) -
Dorrance Anne,
Shea Tim,
Pires Paulo
Publication year - 2014
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.28.1_supplement.853.6
Subject(s) - hypoxia (environmental) , ischemia , mineralocorticoid receptor , medicine , endocrinology , mineralocorticoid , aldosterone , receptor , anesthesia , chemistry , oxygen , organic chemistry
Stroke is a leading cause of death and disability in the US. Cerebral ischemia causes a rapid increase in the circulating levels of the mineralocorticoid aldosterone. We have also shown that mineralocorticoid receptor (MR) antagonism at the time of a stroke reduces the damage caused by ischemia. We know little about how ischemia regulates MR expression. We hypothesized that MR expression is up regulated by hypoxia and that this translates to an increase in MR expression in the ischemic arteries after a stroke. To test the effect of hypoxia on MR expression aortic rings from adult Sprague Dawley rats were incubated under control (normoxic) or hypoxic (1% oxygen) conditions for three hours in the presence or absence of glucose (n=7‐8 in each group). qRT‐PCR was performed to measure MR mRNA expression using TAQMAN probes. Results are expressed as fold change from control. Hypoxia caused a marked increase in MR mRNA expression (1.01±0.06 vs 1.72±0.32, normoxic vs hypoxic p<0.05). Concomitant hypoxia and glucose deprivation had similar effects as hypoxia alone (1.09±0.12 vs 1.84±0.31 normoxia‐glucose vs hypoxia‐glucose p<0.03). To tests the effects of ischemia on vascular MR expression rats underwent a middle cerebral artery (MCA) occlusion (MCAO) for 1 hour followed by 47 hours of reperfusion. The MCA from the ischemic hemisphere was compared to the same artery from sham‐operated rats by qRT‐PCR (n=5‐6). Ischemia caused a marked increase in the MR mRNA expression (in fold change from sham: 1.03±0.11 vs 2.01±0.24 sham vs MCAO, P<0.05). These data suggest that after a stroke the expression of the MR in the vasculature may increase and this may exacerbate the effects of the increase in aldosterone in the aftermath of an acute ischemic stroke. Grant Funding Source : AHA ‐ 13GRNT17210000