Abstract
Aldosterone, a mineralocorticoid, promotes deleterious remodeling of the cardiovascular system. Spironolactone, a non-specific mineralocorticoid receptor (MR) antagonist, prevents remodeling of the middle cerebral artery (MCA) in male spontaneously hypertensive stroke-prone rats (SHRSP). We hypothesized that eplerenone (EPL), a specific MR antagonist, would also prevent remodeling of the MCA of male SHRSP. Six week old male SHRSP were treated with EPL (100 mg/kg/day) for 6 weeks. MCA structure was analyzed using a pressurized arteriograph under passive (calcium-free) conditions from 0 to 180 mmHg. Blood pressure (BP) was measured using telemetry or tail-cuff plethysmography. Lumen and outer diameters were increased (Table) and wall/lumen ratios were decreased (p<0.05, ANOVA) compared to untreated SHRSP; wall area was unchanged (p>0.05, ANOVA), indicating that EPL treatment prevented MCA remodeling. BP was not different between groups (Table), indicating a BP independent effect. In conclusion, the data indicate that effects seen previously with spironolactone are MR specific and highlight the involvement of MR activation in cerebral vessel remodeling.
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