C-type natriuretic peptide (CNP) in the paraventricular nucleus-mediated renal sympatho-inhibition

Volume reflex produces sympatho-inhibition that is mediated by the hypothalamic paraventricular nucleus (PVN). However, the mechanisms for the sympatho-inhibitory role of the PVN and the neurochemical factors involved remain to be identified. In this study, we proposed C-type natriuretic peptide (CNP) as a potential mediator of this sympatho-inhibition within the PVN. Microinjection of CNP (1.0 mu g) into the PVN significantly decreased renal sympathetic nerve activity (RSNA) (-25.8% +/- 1.8% vs. -3.6% +/- 1.5%), mean arterial pressure (-15.0 +/- 1.9 vs. -0.1 +/- 0.9 mmHg) and heart rate (-23.6 +/- 3.5 vs. -0.3 +/- 0.9 beats/min) compared with microinjection of vehicle. Picoinjection of CNP significantly decreased the basal discharge of extracellular single-unit recordings in 5/6 (83%) rostral ventrolateral medulla (RVLM)-projecting PVN neurons and in 6/13 (46%) of the neurons that were not antidromically activated from the RVLM. We also observed that natriuretic peptide receptor type C (NPR-C) was present on the RVLM projecting PVN neurons detected by dual-labeling with retrograde tracer. Prior NPR-C siRNA microinjection into the PVN significantly blunted the decrease in RSNA to CNP microinjections into the PVN. Volume expansion-mediated reduction in RSNA was significantly blunted by prior administration of NPR-C siRNA into the PVN. These results suggest a potential role for CNP within the PVN in regulating RSNA, specifically under physiological conditions of alterations in fluid balance.

Automated summary

In this study, the researchers found that C-type natriuretic peptide (CNP) may serve as a potential mediator of sympatho-inhibition within the hypothalamic paraventricular nucleus (PVN). Microinjection of CNP into the PVN significantly decreased renal sympathetic nerve activity, mean arterial pressure, and heart rate. The effects of CNP on PVN neurons projecting to the rostral ventrolateral medulla (RVLM) were mediated by the natriuretic peptide receptor type C (NPR-C).