Brain microglial cytokines in neurogenic hypertension.
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) 1beta, IL-6, and tumor necrosis factor-alpha, 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-1beta, 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.
Shi
Peng
P
Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL 32610, USA.
Diez-Freire
Carlos
C
Jun
Joo Yun
JY
Qi
Yanfei
Y
Katovich
Michael J
MJ
Li
Qiuhong
Q
Sriramula
Srinivas
S
Francis
Joseph
J
Sumners
Colin
C
Raizada
Mohan K
MK
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001794:Blood Pressure; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D018014:Gene Transfer Techniques; D006339:Heart Rate; D007150:Immunohistochemistry; D007249:Inflammation / Q000503:physiopathology*; D016753:Interleukin-10 / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D008911:Minocycline / Q000494:pharmacology; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000900:Anti-Bacterial Agents; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D016753:Interleukin-10; D008911:Minocycline