Angiotensin II AT1 Receptor Blockade Abolishes Brain Microvascular Inflammation and Heat Shock Protein Responses in Hypertensive Rats
| Autor: | Jin Zhou, Hiromichi Ando, Miroslava Macova, Jingtao Dou, Juan M. Saavedra |
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| Rok vydání: | 2005 |
| Předmět: |
Male
medicine.medical_specialty medicine.drug_class Blood Pressure Receptor Angiotensin Type 1 Proinflammatory cytokine Brain ischemia Heat Shock Transcription Factors Internal medicine Heat shock protein Renin–angiotensin system Animals Medicine RNA Messenger Receptor Heat-Shock Proteins Inflammation Tumor Necrosis Factor-alpha business.industry Macrophages Microcirculation NF-kappa B Transcription Factor RelA Brain Receptor antagonist medicine.disease Angiotensin II Rats DNA-Binding Proteins Candesartan Endocrinology Gene Expression Regulation Neurology Hypertension Encephalitis Neurology (clinical) Cardiology and Cardiovascular Medicine business Angiotensin II Type 1 Receptor Blockers Interleukin-1 Transcription Factors medicine.drug |
| Zdroj: | Journal of Cerebral Blood Flow & Metabolism. 25:878-886 |
| ISSN: | 1559-7016 0271-678X |
| DOI: | 10.1038/sj.jcbfm.9600082 |
| Popis: | Endothelial dysfunction and inflammation enhance vulnerability to hypertensive brain damage. To explore the participation of Angiotensin II (Ang II) in the mechanism of vulnerability to cerebral ischemia during hypertension, we examined the expression of inflammatory factors and the heat shock protein (HSP) response in cerebral microvessels from spontaneously hypertensive rats and their normotensive controls, Wistar Kyoto rats. We treated animals with vehicle or the Ang II AT1 receptor antagonist candesartan, 0.3 mg/kg/day, via subcutaneously implanted osmotic minipumps for 4 weeks. Spontaneously hypertensive rats expressed higher Angiotensin II AT1 receptor protein and mRNA than normotensive controls. Candesartan decreased the macrophage infiltration and reversed the enhanced tumor necrosis factor-α and interleukin-1β mRNA and nuclear factor-κB in microvessels in hypertensive rats. The transcription of many HSP family genes, including HSP60, HSP70 and HSP90, and heat shock factor-1 was higher in hypertensive rats and was downregulated by AT1 receptor blockade. Our results suggest a proinflammatory action of Ang II through AT1 receptor stimulation in cerebral microvessels during hypertension, and very potent antiinflammatory effects of the Ang II AT1 receptor antagonist. These compounds might be considered as potential therapeutic agents against ischemic and inflammatory diseases of the brain. |
| Databáze: | OpenAIRE |
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