Vascular protection with candesartan after experimental acute stroke in hypertensive rats: A dose-response study

Wieslaw Kozak, Anna Kozak, Maribeth H. Johnson, Hazem F. Elewa, Susan C. Fagan

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

We have shown that candesartan decreases the acute stroke-induced elevation of mean arterial blood pressure (MAP) in Wistar rats and improves functional outcome. The aim of the present study was to determine whether the same benefit could be achieved in spontaneously hypertensive rats (SHR). Animals were subjected to middle cerebral artery occlusion (MCAO) or sham for 3 h followed by reperfusion. Either candesartan (0.1, 0.3, or 1.0 mg/kg) or saline was administered. MAP of the rats was monitored by means of telemetry, and neurological function was assessed. Infarct size, edema formation, and hemoglobin content in the ischemic hemisphere were evaluated 24 h after the stroke. MAP of SHR increased immediately upon MCAO from 135 (baseline) to 189 mm Hg, and it remained elevated until reperfusion. Candesartan decreased MAP in a dose-dependent manner, with a drop below baseline after a dose of 1.0 mg/kg. SHRs experienced greater blood pressure (BP)-lowering effects of candesartan after stroke compared with a sham condition (p < 0.0001). Neurological deficit after stroke was reduced in candesartan-treated animals, revealing a dose-dependent effect (p < 0.01). Infarct size, edema formation, and hemoglobin content were all reduced by candesartan at doses of 0.1 and 0.3 mg/kg (p < 0.05 for all). Candesartan (1 mg/kg) was not different from saline. Low doses of candesartan provide neurovascular protection after stroke in SHRs. Caution is warranted because acute stroke increases the sensitivity to BP lowering, which, in turn, increases the likelihood of over-shooting.

Original languageEnglish (US)
Pages (from-to)773-782
Number of pages10
JournalJournal of Pharmacology and Experimental Therapeutics
Volume326
Issue number3
DOIs
StatePublished - Sep 1 2008

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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