Vascular protection with candesartan after experimental acute stroke in hypertensive rats: a dose-response study.
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 overshooting.
Kozak
Wieslaw
W
Institute of General and Molecular Biology, Nicolas Copernicus University, Torun, Poland.
Kozak
Anna
A
Johnson
Maribeth H
MH
Elewa
Hazem F
HF
Fagan
Susan C
SC
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D020521:Stroke / Q000503:physiopathology / Q000517:prevention & control*; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*
D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C081643:candesartan