Angiotensin II Type 2 Receptor Stimulation Initiated After Stroke Causes Neuroprotection in Conscious RatsNovelty and Significance
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We have demonstrated previously that pretreatment with an angiotensin II type 2 receptor (AT2R) agonist is neuroprotective against a subsequent stroke independent of any changes in blood pressure. Therefore, in the current study, we have examined the potential neuroprotective effect of AT2R stimulation initiated after stroke induction to mimic the clinical setting. Intracerebroventricular administration of the AT2R agonist CGP42112 was commenced 6 hours after an ischemic stroke had been induced in conscious spontaneously hypertensive rats. CGP42112 given over 4 doses in the same rats (3 µg/kg per dose centrally) at 6, 24, 48, and 72 hours after stroke induction reduced total infarct volume (32±13 mm3 versus vehicle, 170±49 mm3; P<0.05) and improved motor function. Furthermore, we have demonstrated that AT2R stimulation after stroke increased neuronal survival, decreased apoptosis, and caused an increase in the number of activated microglia in the core region of damage. The effects of CGP42112 were partially reversed with the coadministration of an AT2R antagonist, PD123319. Thus, the current study has shown for the first time that delayed central AT2R stimulation after a cerebral incident is neuroprotective in a conscious rat model of stroke.
- Received May 30, 2012.
- Revision received June 19, 2012.
- Accepted September 1, 2012.
- © 2012 American Heart Association, Inc.