Renal Denervation Improves Exaggerated Sympathoexcitation in Rats With Heart Failure: A Role for Neuronal Nitric Oxide Synthase in the Paraventricular Nucleus.

Abstract

Renal denervation (RDN) has been postulated to reduce sympathetic drive during heart failure (HF), but the central mechanisms are not completely understood. The purpose of the present study was to assess the contribution of neuronal nitric oxide synthase (nNOS) within the paraventricular nucleus (PVN) in modulating sympathetic outflow in rats with HF that underwent RDN. HF was induced in rats by ligation of the left coronary artery. Four weeks after surgery, bilateral RDN was performed. Rats with HF had an increase in FosB-positive cells in the PVN with a concomitant increase in urinary excretion of norepinephrine, and both of these parameters were ameliorated after RDN. nNOS-positive cells immunostaining, diaphorase staining, and nNOS protein expression were significantly decreased in the PVN of HF rats, findings that were ameliorated by RDN. Microinjection of nNOS inhibitor N(G)-monomethyl l-arginine into the PVN resulted in a blunted increase in lumbar sympathetic nerve activity (11±2% versus 24±2%) in HF than in sham group. This response was normalized after RDN. Stimulation of afferent renal nerves produced a greater activation of PVN neurons in rats with HF. Afferent renal nerve stimulation elicited a greater increase in lumbar sympathetic nerve activity in rats with HF than in sham rats (45±5% versus 22±2%). These results suggest that intact renal nerves contribute to the reduction of nNOS in the PVN, resulting in the activation of the neurons in the PVN of rats with HF. RDN restores nNOS and thus attenuates the sympathoexcitation commonly observed in HF.

• Authors: Kaushik P Patel, Bo Xu, Xuefei Liu, Neeru M Sharma, Hong Zheng
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 68 Issue 1 Pg. 175-84 (07 2016) ISSN: 1524-4563 [Electronic] United States
• PMID: 27185748 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2016 American Heart Association, Inc.

Chemical References

• Nitric Oxide Synthase Type I

Topics

• Animals
• Autonomic Denervation (methods)
• Disease Models, Animal
• Heart Failure (metabolism, physiopathology)
• Kidney (innervation, surgery)
• Male
• Nitric Oxide Synthase Type I (metabolism)
• Paraventricular Hypothalamic Nucleus (metabolism)
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Reference Values
• Sympathetic Nervous System (physiopathology)