AT1 Receptor Blocker Candesartan-induced Attenuation of Brain Injury of Rats Subjected to Chronic Cerebral Hypoperfusion

Abstract

One of common pathophysiological states associated with central nervous system is chronic cerebral hypoperfusion (CH) that frequently occurs in conditions such as vascular dementia and Alzheimer's disease. Long term blockage of angiotensin II type 1 (AT(1)) receptor provides protection from ischemia induced injury of brain as well as reduction of cerebrovascular inflammation. Examining effect of the blockage on reduced glutathione (GSH), ascorbic acid (AA), and lipid peroxidation were of purpose in the present study. Modeling CH, rats were subjected to permanent occlusion of common carotid arteries bilaterally. AT(1 )receptor antagonist, candesartan, was given daily for 14 days after surgery. CH caused a significant increase in lipid peroxidation and decrease in GSH content of cerebral hippocampal tissue with no change in AA level. Candesartan (0.5 mg/kg, oral) not only reduced lipid peroxidation but also restored GSH significantly besides elevating AA and improving histopathological alterations. In conclusion, long term AT(1 )receptor blockage may be considered as novel therapeutic approach for protection from damage associated with CH. Underlying mechanism(s) may in part be related to suppressing oxidative stress and preserving brain antioxidant capacity.

Angiotensin II AT1 Receptor Blockers Ameliorate Inflammatory Stress: A Beneficial Effect for the Treatment of Brain Disorders

“…Conversely, anti-anxiety effects of ARBs, of potency similar to that of benzodiazepines, and antidepressant effects in mice and rats have been reported by other groups (Kaiser et al 1992; Gard et al 2001; Shekhar et al 2006). Other pre-clinical studies on stroke models confirmed our initial observations of the neuroprotective, anti-inflammatory effects of ARBs (Ozacmak et al 2007; Hallevi et al 2007; Jung et al 2007). These studies also substantiated our hypothesis of beneficial effects of ARBs unrelated to hypertension (Sironi et al 2004), because they demonstrated that ARBs protect from experimental stroke in normotensive animals (Lou et al 2004).…”

The neuron-astrocyte-microglia triad in CA3 after chronic cerebral hypoperfusion in the rat: Protective effect of dipyridamole

“…Brain chronic hypoperfusion, caused by partial carotid occlusion during aging, represents a chronic, dynamic process that causes multiple progressive alterations, and eventually leads to neurodegeneration (Ozacmak et al 2007;Farkas et al 2007) and vascular dementia (Chmayssani et al 2007). The CA1 region of the hippocampus results particularly vulnerable to decreased blood flow and glucose supply caused by 2VO occlusion, that cause failure of neuronal signaling, and impairments in hippocampally-based forms of memory (De Jong et al 1999;Liu et al 2005;Farkas et al 2006;Melani et al 2010;Lana et al 2013).…”

The neuron-astrocyte-microglia triad in a rat model of chronic cerebral hypoperfusion: protective effect of dipyridamole

“…Brain chronic hypoperfusion, caused in the elderly by partial carotid occlusion, is a progressive, dynamic process that causes multiple alterations as ischemic conditions persist, leading to neurodegeneration (Farkas et al, 2007; Ozacmak et al, 2007) and vascular dementia (Chmayssani et al, 2007). …”