NEUROPHARMACOLOGY AND NEUROTOXICOLOGYNeuroprotective effects of candesartan against cerebral ischemia in spontaneously hypertensive ratsLu, Qing; Zhu, Yi-Zhun; Wong, Peter T.-H.Author Information Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore Correspondence and requests for reprints to Dr Peter T.-H. Wong, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 18 Medical Drive, Singapore 117597, Singapore Tel: +65 6874 3224; fax: +65 6873 7690; e-mail: [email protected] Sponsorship: This work was supported by research grants from the National Medical Research Council of Singapore (R-184-000-066-213) and the National University of Singapore (G-6655). Received 15 August 2005; revised 23 September 2005; accepted 24 September 2005 NeuroReport: November 28, 2005 - Volume 16 - Issue 17 - p 1963-1967 doi: 10.1097/01.wnr.0000187636.13147.cd Buy Metrics Abstract The cerebral protective effects of 4-week treatment with candesartan (0.3, 1, 3 mg/kg/day) and ramipril (0.5, 1.5, 5 mg/kg/day) were examined in spontaneous hypertensive rats 24 h after middle cerebral artery occlusion. We found that both candesartan and ramipril could reduce the infarct volume and neurological deficit scores compared with control. Importantly, the neuroprotective effects of candesartan (1 mg/kg/day) were abolished by PD123319 (an AT2 receptor antagonist, 10 mg/kg/day). AT1 receptor gene expression was downregulated while AT2 receptor gene expression was upregulated by candesartan. It is concluded that candesartan appears to provide beneficial effects against stroke in spontaneous hypertensive rats in three ways: AT1 receptor antagonism, downregulation of AT1 receptor expression and upregulation of AT2 receptor expression. © 2005 Lippincott Williams & Wilkins, Inc.