ANGIOTENSIN AT(2) RECEPTOR STIMULATION INCREASES SURVIVAL IN GERBILS WITH ABRUPT UNILATERAL CAROTID LIGATION

Previous studies showed that angiotensin II (AII) infusion increased s urvival in gerbils subjected to abrupt unilateral carotid ligation. Re cently, stimulation of the AII AT, receptor, reportedly effectively ex tended the blood pressure (BP) range of cerebral blood flow (CBF) auto regulation. We evaluated the survival of gerbils treated with PD-12331 9, a ligand of AT(2) receptors, to test the hypothesis that restoratio n of BF to ischemic cerebral tissue produced by AII is mediated throug h AT, receptors. Abrupt unilateral carotid ligation was performed on 3 00 gerbils. In five experimental groups, animals received no drug pret reatment: (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 improv ed 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 AT(2) agonist and improved survival in this animal model of stro ke. Losartan, an AT(1) antagonist, also improved survival, possibly th rough renin release and AT(2) stimulation by endogenous AII. This effe ct was neutralized by enalaprilat.