Previous studies showed that
angiotensin II (AII) infusion increased survival in gerbils subjected to abrupt unilateral carotid
ligation. Recently, stimulation of the AII AT2 receptor, reportedly effectively extended the blood pressure (BP) range of cerebral blood flow (CBF) autoregulation. We evaluated the survival of gerbils treated with
PD-123319, a
ligand of AT2 receptors, to test the hypothesis that restoration of BF to ischemic cerebral tissue produced by AII is mediated through AT2 receptors. Abrupt unilateral carotid
ligation was performed on 300 gerbils. In five experimental groups, animals received no
drug pretreatment: (a) saline; (b)-(d)
PD-123319 1.0, 3.0, and 10 mg/kg; and (e)
losartan 10 mg/kg. In three additional experimental groups, animals were pretreated with
enalaprilat: (f) saline; (g)
PD-123319, 10 mg/kg, and (h)
losartan, 10 mg/kg. Survival for 48 h was significantly improved by
PD-123319 (10 mg/kg) (p < 0.05) and by
losartan (10 mg/kg) (p < 0.05) as compared with animals injected with saline. Pretreatment with
enalaprilat neutralized the protective effect of
losartan.
PD-123319 is an AT2 agonist and improved survival in this animal model of
stroke.
Losartan, an AT1 antagonist, also improved survival, possibly through
renin release and AT2 stimulation by endogenous AII. This effect was neutralized by
enalaprilat.