期刊
HYPERTENSION
卷 78, 期 5, 页码 1450-1462出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/HYPERTENSIONAHA.121.18219
关键词
angiotensin II; autonomic nervous system; blood pressure; cytokines; hemodynamics; paraventricular hypothalamic nucleus
资金
- National Institutes of Health [R01 HL-139521, HL-155091, HL-139575]
- University of Iowa
IL-17A in the brain promotes neuroinflammation to advance sympathetic activation and hypertension, probably by a synergistic mechanism involving the interaction with various inflammatory mediators within the brain.
IL (Interleukin)-17A is a key inflammatory mediator contributing to chronic tissue inflammation. The present study sought to determine whether IL-17A plays a role in regulating neuroinflammation, hemodynamics, and sympathetic outflow in normal and hypertensive animals. In urethane-anesthetized rats, intravenous injection of IL-17A induced dramatic and prolonged increases in blood pressure, heart rate, and renal sympathetic nerve activity, which were significantly attenuated by an IL-17RA (IL-17 receptor A) siRNA in the hypothalamic paraventricular nucleus (PVN). Either intracerebroventricular or PVN microinjection of IL-17A also elicited a similar excitatory response in blood pressure, heart rate, and renal sympathetic nerve activity. Intravenous injection of IL-17A upregulated the mRNA level of IL-17A, IL-17F, and IL-17RA in the PVN. Additionally, intravenous injection of IL-17A activated brain-resident glial cells and elevated the gene expression of inflammatory cytokines and chemokines in the PVN, which were markedly diminished by PVN microinjection of IL-17RA siRNA. Pretreatments with microglia or astrocyte inhibitors attenuated the increase in blood pressure, heart rate, and renal sympathetic nerve activity in response to PVN IL-17A. Moreover, intracerebroventricular injection of IL-17A activated TGF (transforming growth factor)-beta activated kinase 1, p44/42 mitogen-activated protein kinase, and transcriptional nuclear factor kappa B in the PVN. IL-17A interacted with tumor necrosis factor-alpha or IL-1 beta synergistically to exaggerate its influence on hemodynamic and sympathetic responses. Central intervention suppressing IL-17RA in the PVN significantly reduced angiotensin II-induced hypertension, neuroinflammation, and sympathetic tone in the rats. Collectively, these data indicated that IL-17A in the brain promotes neuroinflammation to advance sympathetic activation and hypertension, probably by a synergistic mechanism involving the interaction with various inflammatory mediators within the brain.
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