Received for publication April 4, 2008.
Revised June 16, 2008.
Accepted for publication June 16, 2008.

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

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). METHODS. Animals were subjected to middle cerebral artery occlusion (MCAO) or sham for 3 hours followed by reperfusion. Either candesartan 0.1 mg/kg, 0.3 mg/kg, 1.0 mg/kg or saline were administered. MAP of the rats was monitored by means of telemetry and neurologic function was assessed. Infarct size, edema formation and hemoglobin content in the ischemic hemisphere were evaluated 24 h after the stroke. RESULTS. MAP of SHR increased immediately upon MCAO from 135 (baseline) to 189 mmHg, and 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 were experienced greater BP lowering effects of candesartan after stroke compared with a sham condition (p<0.0001). Neurologic 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. CONCLUSION. Low doses of candesartan provide neurovascular protection after stroke in SHRs. Caution is warranted since acute stroke increases the sensitivity to BP lowering, increasing the likelihood of overshooting.

Key words: candesartan, hemorrhage, hypertension, rat, stroke, telemetry