Published Online
on March 4, 2004

A more recent version of this article appeared on April 1, 2004

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Submitted on November 27, 2003
Accepted on December 29, 2003

Cerebral Ischemia Enhances Vascular Angiotensin AT₁ Receptor-Mediated Contraction in Rats

Emelie Stenman MSc^* and Lars Edvinsson MD, PhD

From the Division of Experimental Vascular Research, Department of Internal Medicine, Lund University, Lund, Sweden.

^* To whom correspondence should be addressed. E-mail: Emelie.Stenman{at}med.lu.se.

Background and Purpose--The aim of the study was to examine how focal cerebral ischemia affects the expression and function of vascular angiotensin II receptors.

Materials and Methods--We used an intraluminal filament occlusion technique to occlude the right middle cerebral artery (MCA) of the rat. Myographs were used for functional studies of the MCA and real-time polymerase chain reaction, for determination of relative mRNA levels.

Results--The contractile responses to angiotensin II were stronger in the right occluded MCA compared with the left MCA and the MCA from sham-operated rats 48 hours after MCA occlusion (P<0.05). The angiotensin II type 1 (AT₁) receptor antagonists candesartan and losartan abolished the enhanced responses to angiotensin II (P<0.05), whereas the AT₂ receptor antagonist PD123319 had no effect. The amount of AT₁ receptor mRNA was lower in the occluded MCAs compared with nonoccluded MCAs 48 hours after occlusion (P<0.05), whereas the mRNA levels of angiotensin converting enzyme (ACE) were higher in the occluded arteries. The mRNA levels of the AT₂ receptor and nuclear factor-B were unchanged.

Conclusions--Focal cerebral ischemia in the rat upregulated the contractile responses to angiotensin II in the ipsilateral MCA, and this contraction was mediated by AT₁ receptors. Real-time polymerase chain reaction revealed decreased AT₁ receptor mRNA levels in the occluded MCA, whereas the amount of ACE mRNA was increased, suggesting locally enhanced angiotensin II production. These results support a role for AT₁ receptors in cerebral ischemia, and we think that AT₁ receptors might be a future therapeutic target in ischemic stroke.

Key words: angiotensins • receptors, angiotensin • angiotensin converting enzyme inhibitors • cerebral ischemia

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