Angiotensin II Type 1a Receptors in the Subfornical Organ Modulate Neuroinflammation in the Hypothalamic Paraventricular Nucleus in Heart Failure Rats

Publication date: 15 June 2018 Source:Neuroscience, Volume 381 Author(s): Yang Yu, Shun-Guang Wei, Robert M. Weiss, Robert B. Felder Inflammation in the hypothalamic paraventricular nucleus (PVN) contributes to neurohumoral excitation and its adverse consequences in systolic heart failure (HF). The stimuli that trigger inflammation in the PVN in HF are not well understood. Angiotensin II (AngII) has pro-inflammatory effects, and circulating levels of AngII increase in HF. The subfornical organ (SFO), a circumventricular structure that lacks an effective blood–brain barrier and senses circulating AngII, contains PVN-projecting neurons. We hypothesized that activation of AngII type 1a receptors (AT1aR) in the SFO induces neuroinflammation downstream in the PVN. Male rats received SFO microinjections of an adeno-associated virus carrying shRNA for AT1aR, a scrambled shRNA, or vehicle. One week later, some rats were euthanized to confirm the transfection potential and knockdown efficiency of the shRNA. Others underwent coronary artery ligation to induce HF or a sham coronary artery ligation (Sham). Four weeks later, HF rats that received the scrambled shRNA had increased mRNA in SFO and PVN for AT1aR, inflammatory mediators and indicators of neuronal and glial activation, increased plasma levels of AngII, tumor necrosis factor-α, norepinephrine and arginine vasopressin, and impaired cardiac function, compared with Sham rats that received scrambled shRNA. The central abno...

Source: Neuroscience - May 3, 2018 Category: Neuroscience Source Type: research