Hypoxia-Inducible Factor-1 alpha Mediates Increased Sympathoexcitation via Glutamatergic N-Methyl-D-Aspartate Receptors in the Paraventricular Nucleus of Rats With Chronic Heart Failure

摘要

Background-Increased sympathetic outflow is a major contributor to the progression of chronic heart failure (CHF). Potentiation of glutamatergic tone has been causally related to the sympathoexcitation in CHF. Specifically, an increase in the N-methyl-D-aspartate-type 1 receptor (NMDA-NR1) expression within the paraventricular nucleus (PVN) is critically linked to the increased sympathoexcitation during CHF. However, the molecular mechanism(s) for the upregulation of NMDA-NR1 remains unexplored. We hypothesized that hypoxia via hypoxia-inducible factor 1 alpha (HIF-1 alpha) might contribute to the augmentation of the NMDA-NR1-mediated sympathoexcitatory responses from the PVN in CHF.