Upregulation of Chemokines in the Paraventricular Nucleus of the Hypothalamus in Rats with Stress-Induced Hypertension

Med Sci Monit. 2020 Nov 17:26:e926807. doi: 10.12659/MSM.926807.


BACKGROUND The neuroinflammation of paraventricular nucleus (PVN) of the hypothalamus has been implicated in the development of hypertension. The promoted invasion of peripheral immune cells into PVN may be attributed to the upregulation of chemokines, then exacerbating neuroinflammation. We studied the expressions of chemokines, activation of microglial cells, and inflammatory mediators in PVN of rats with stress-induced hypertension (SIH). MATERIAL AND METHODS SIH was induced by electrical foot shock combined with noise for 2 h twice a day, at an interval of 4 h for 14 consecutive days. At the end of the 14th day, fresh PVN tissues were collected to measure the expressions of chemokines using the RayBiotech antibody array. RESULTS We are the first to report that the expression of CXCL7 was extremely high in PVN of control rats, and was significantly lower in SIH rats. The expressions of CCL2 and CX3CL1 in PVN of SIH rats significantly exceeded those of control rats. The numbers of CX3CR1 (receptor of CX3CL1)-immunostained cells and oxycocin-42 (OX-42, marker of microglia)-positive cells increased in PVN of the SIH rats. The stress enhanced the protein expressions of proinflammatory cytokines IL-6 and IL-17 and reduced those of anti-inflammatory cytokines TGF-ß and IL-10 in PVN. CONCLUSIONS In PVN of SIH rats, chronic stress induced neuroinflammation characterized by the activated microglia and upregulated proinflammatory cytokines. Expressions of chemokines CXCL7, CX3CL1, and CCL2 were altered. The causal link of chemokines to PVN neuroinflammation and hypertension remain to be determined.

MeSH terms

  • Animals
  • Blood Pressure / physiology
  • Chemokines / genetics*
  • Chemokines / metabolism
  • Heart Rate / physiology
  • Hypertension / etiology*
  • Hypertension / genetics*
  • Hypertension / physiopathology
  • Inflammation Mediators / metabolism
  • Male
  • Microglia / pathology
  • Paraventricular Hypothalamic Nucleus / pathology*
  • Paraventricular Hypothalamic Nucleus / physiopathology
  • Rats, Sprague-Dawley
  • Stress, Psychological / complications*
  • Stress, Psychological / physiopathology
  • Up-Regulation / genetics*


  • Chemokines
  • Inflammation Mediators