Spironolactone reduces cerebral infarct size and EGF-receptor mRNA in stroke-prone rats

Anne M. Dorrance, Heather L. Osborn, Roger Grekin, R. Clinton Webb

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Abstract

Remodeling of the cerebral vasculature contributes to the pathogenesis of cerebral ischemia. Remodeling is caused by increased smooth muscle proliferation and may be due to an increase in the responsiveness of vascular cells to epidermal growth factor (EGF). Aldosterone is a risk factor for stroke, and the literature suggests it may play a role in increasing the expression of the receptor for EGF (EGFR). We hypothesized that mRNA for the EGF-stimulated pathway would be elevated in the vasculature of stroke-prone spontaneously hypertensive rats (SHRSP) and that this and experimental ischemic cerebral infract size would be reduced by aldosterone inhibition with spironolactone. We found that spironolactone treatment reduced the size of cerebral infarcts after middle cerebral artery occlusion in SHRSP (51.69 ± 3.60 vs. 22.00 ± 6.69% of hemisphere-infarcted SHRSP vs. SHRSP + spironolactone P < 0.05). Expression of EGF and EGFR mRNA was higher in cerebral vessels and aorta from adult SHRSP compared with Wistar-Kyoto rats. Only the expression of EGFR mRNA was elevated in the young SHRSP. Spironolactone reduced the EGFR mRNA expression in the aorta (1.09 ± 0.25 vs. 0.56 ± 0.11 phosphorimage units SHRSP vs. SHRSP + spironolactone P < 0.05) but had no effect on EGF mRNA. In vitro incubation of aorta with aldosterone ± spironolactone produced similar results, suggesting a direct effect of aldosterone. Thus spironolactone may reduce the size of cerebral infarcts via a reduction in the expression of the EGFR mRNA, leading to reduced remodeling.

Original languageEnglish (US)
Pages (from-to)R944-R950
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume281
Issue number3 50-3
StatePublished - Oct 3 2001

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Keywords

  • Cerebral ischemia
  • Hypertension
  • Mineralocorticoid

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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