Brain Microglial Cytokines in Neurogenic Hypertension

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 56; no. 2; pp. 297 - 303
• Main Authors: Shi, Peng, Diez-Freire, Carlos, Jun, Joo Yun, Qi, Yanfei, Katovich, Michael J., Li, Qiuhong, Sriramula, Srinivas, Francis, Joseph, Sumners, Colin, Raizada, Mohan K.
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 01.08.2010; Lippincott Williams & Wilkins
• Subjects: Angiotensin II - antagonists & inhibitors; Angiotensin II - pharmacology; Animals; Anti-Bacterial Agents - pharmacology; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure; Brain - drug effects; Brain - metabolism; Brain - physiopathology; Cardiology. Vascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Cytokines - blood; Cytokines - genetics; Cytokines - metabolism; Gene Transfer Techniques; Heart Rate; Immunohistochemistry; Inflammation - physiopathology; Interleukin-10 - genetics; Interleukin-1beta - genetics; Interleukin-6 - genetics; Male; Medical sciences; Microglia - drug effects; Microglia - metabolism; Minocycline - pharmacology; Prosencephalon - drug effects; Prosencephalon - metabolism; Prosencephalon - physiopathology; Rats; Rats, Sprague-Dawley; RNA, Messenger - genetics; Tumor Necrosis Factor-alpha - genetics; Hypertension; Tetracycline derivatives; Interleukin; Peptide hormone; Cytokine; Cardiovascular disease; Paraventricular nucleus; Encephalon; Octapeptide; Antibiotic; Minocycline; Protein synthesis inhibitor; Angiotensin II; Antibacterial agent; microglia; interleukin 10
• ISSN: 0194-911X; 1524-4563; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.110.150409

Accumulating evidence indicates a key role of inflammation in hypertension and cardiovascular disorders. However, the role of inflammatory processes in neurogenic hypertension remains to be determined. Thus, our objective in the present study was to test the hypothesis that activation of microglial cells and the generation of proinflammatory cytokines in the paraventricular nucleus (PVN) contribute to neurogenic hypertension. Intracerebroventricular infusion of minocycline, an anti-inflammatory antibiotic, caused a significant attenuation of mean arterial pressure, cardiac hypertrophy, and plasma norepinephrine induced by chronic angiotensin II infusion. This was associated with decreases in the numbers of activated microglia and mRNAs for interleukin (IL) 1β, IL-6, and tumor necrosis factor-α, and an increase in the mRNA for IL-10 in the PVN. Overexpression of IL-10 induced by recombinant adenoassociated virus-mediated gene transfer in the PVN mimicked the antihypertensive effects of minocycline. Furthermore, acute application of a proinflammatory cytokine, IL-1β, into the left ventricle or the PVN in normal rats resulted in a significant increase in mean arterial pressure. Collectively, this indicates that angiotensin II induced hypertension involves activation of microglia and increases in proinflammatory cytokines in the PVN. These data have significant implications on the development of innovative therapeutic strategies for the control of neurogenic hypertension.