Interaction Between Interleukin-1 Beta and Angiotensin II Receptor 1 in Hypothalamic Paraventricular Nucleus Contributes to Progression of Heart Failure

The central mechanisms by which interleukin-1 beta (IL-1 beta) and angiotension II receptor 1 (AT1-R) contribute to sympathoexcitation in heart failure (HF) are unclear. In this study, we determined whether an interaction between IL-1 beta and AT1-R in the paraventricular nucleus (PVN) contributes to progression of HF. Rats were implanted with bilateral PVN cannulae and subjected to coronary artery ligation or sham surgery (Sham). Subsequently, animals were treated for 4 weeks through PVN infusion with either vehicle, losartan (LOS, 200 mu g/day), IL-1 beta (IL, 1 mu g/day), or IL-1 beta along with LOS (LOS+IL). HF rats had higher levels of corticotropin-releasing hormone (CRH), norepinephrine (NE), and glutamate (Glu); lower levels of gamma-aminobutyric acid (GABA); and more positive fra-like activity in PVN when compared with Sham rats. HF rats also had higher levels of NE, epinephrine (EPI), and IL-1 beta in plasma. PVN infusion of LOS attenuated the decreases in GABA and the increases in CRH, NE, and Glu in the PVN of HF rats. IL-1 beta could further increase the expression of CRH, NE, Glu, EPI, and IL-1 beta and decrease GABA expression. Treatment with IL-1 beta along with LOS could eliminate the effects of IL-1 beta. These findings suggest that an interaction between AT1-R and IL-1 beta in the PVN contributes to progression in HF.