Upregulation of pro‐inflammatory cytokine receptors in forebrain subfornical organ and hypothalamic paraventricular nucleus in rats with heart failure (686.23)

Abstract

The pro‐inflammatory cytokines tumor necrosis factor‐α (TNF‐α) and interleukin (IL)‐1β play an important role in regulating sympathetic drive and neuroendocrine activation in heart failure (HF). Previous studies in normal rats have demonstrated that receptors for TNF‐α and IL‐1β are abundant in the subfornical organ (SFO) but only sparsely expressed in the hypothalamic paraventricular nucleus (PVN). In HF rats, TNF‐α and IL‐1β increase in the circulation and in cardiovascular autonomic regions of the brain. Pro‐inflammatory cytokines can upregulate their own receptors, but the question of whether TNF‐α and IL‐1β receptors increase in SFO or PVN in HF has not been addressed. We examined TNF‐α and IL‐1β receptor (IL‐1RAcP component) expression in SFO and PVN in adult male Srague‐Dawley rats 4‐5 weeks after myocardial infarction or sham operation (Sham), using immunofluorescent staining and real‐time PCR analysis. Fluorescent intensity for TNF‐α and IL‐1β receptors was significantly (*p<0.05, n=6) greater in both SFO and PVN in the HF rats, compared with Sham rats. Similarly, the mRNA levels of TNF‐α and IL‐1β receptors in SFO and PVN were significantly (n=5) higher in HF compared with Sham rats. These data indicate that upregulation of TNF‐α and IL‐1β receptors contributes to the inflammatory state driving sympathetic and neuroendocrine activity in these key cardiovascular autonomic regions of the brain in HF.Grant Funding Source: Supportd by NIH R01HL073986