Journal
HYPERTENSION
Volume 60, Issue 6, Pages 1531-U396Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/HYPERTENSIONAHA.112.199646
Keywords
angiotensin II type 2 receptors; angiotensin; stroke; hypertension
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Funding
- Australian Postgraduate Award
- Monash University Faculty of Medicine
- National Health and Medical Research Council (NHMRC) of Australia [APP1007986]
- CASS Foundation
- Monash University Larkins Fellowship
- Heart Foundation (Australia)
- Foundation for High Blood Pressure Research Postdoctoral Fellowship
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We have demonstrated previously that pretreatment with an angiotensin II type 2 receptor (AT(2)R) 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 AT(2)R stimulation initiated after stroke induction to mimic the clinical setting. Intracerebroventricular administration of the AT(2)R 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 mu g/kg per dose centrally) at 6, 24, 48, and 72 hours after stroke induction reduced total infarct volume (32 +/- 13 mm(3) versus vehicle, 170 +/- 49 mm(3); P<0.05) and improved motor function. Furthermore, we have demonstrated that AT(2)R 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 AT(2)R antagonist, PD123319. Thus, the current study has shown for the first time that delayed central AT(2)R stimulation after a cerebral incident is neuroprotective in a conscious rat model of stroke. (Hypertension. 2012;60:1531-1537.)
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