Interaction between interleukin‑6 and angiotensin II receptor 1 in the hypothalamic paraventricular nucleus contributes to progression of heart failure.

The association between interleukin-6 (IL-6) and angiotensin II receptor 1 (AT1-R) in modulating the progression of heart failure (HF) remains to be fully elucidated. The aim of the present study was to investigate the mechanism of IL-6 and AT1-R in a model of HF induced by surgery. Male Sprague-Dawley rats were randomly divided into five groups, including sham surgery and vehicle groups. The animals were treated for 4 weeks via paraventricular nucleus infusion with either vehicle, losartan (LOS; 200 mu g/day), IL-6 (1 mu g/day) or LOS and IL-6 together (LOS+ IL-6). The rats with HF had higher levels of IL-6, corticotropin-releasing hormone (CRH) and norepinephrine (NE), and a lower level of neuronal nitric oxide synthase (nNOS), compared with the rats in the sham surgery group. Treatment with LOS attenuated the decrease in nNOS and the increases in IL-6, CRH and NE; whereas treatment with IL-6 facilitated the lower expression of nNOS and higher expression levels of IL-6, CRH and NE. No differences in the expression levels of nNOS, CRH or NE were found between the LOS group and LOS+ IL-6 group. The results of the study demonstrated that IL-6 contributed to the progression of HF via the AT1-R pathway.