ENOS contributes to altered nitric oxide availability and neuronal activity in the PVN during Heart Failure

Abstract

An altered nitric oxide (NO) function within the hypothalamic paraventricular nucleus (PVN) is involved in increased neurohumoral drive during heart failure (HF). However, the precise cellular sources and NOS isoforms involved are still unknown. Here, we evaluated the expression, and functional relevance of the endothelial NOS isoform (eNOS) within the PVN of HF rats. Our studies indicate eNOS expression in astrocytes and the local microvasculature, but not in major PVN neurons. A diminished eNOS signal was apparent in the PVN of HF rats. Studies using the NO‐sensitive dye DAF2 indicated diminished NO levels in the posterior parvocellular subnucleus (13%, P<0.001), an area containing presympathetic PVN neurons. While the specific eNOS blocker L‐NIO (10 μM) diminished DAF2 levels in sham rats (14%, P<0.05) within this region, no changes were observed in HF rats. No differences in NO availability or L‐NIO effects were observed in magnocellular regions of the PVN and SON (P>0.1). L‐NIO increased the firing discharge of PVN‐RVLM neurons in sham rats (∼75%, P< 0.02), an effect that was blunted in PVN‐RVLM neurons from HF rats (P>0.1). In summary, our results support that a diminished eNOS expression/function within autonomic‐related PVN regions contributes to enhanced PVN neuronal activity, and likely neurohumoral activation, during HF. AHA 0640092N and NIH HL68725.