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

Kaushik P. Patel, Bo Xu, Xuefei Liu, Neeru M. Sharma, Hong Zheng

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 NG-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.

Original languageEnglish (US)
Pages (from-to)175-184
Number of pages10
JournalHypertension
Volume68
Issue number1
DOIs
StatePublished - Jul 1 2016

Fingerprint

Nitric Oxide Synthase Type I
Paraventricular Hypothalamic Nucleus
Denervation
Heart Failure
Kidney
Neurons
Microinjections
Ligation
Arginine
Coronary Vessels
Norepinephrine
Staining and Labeling

Keywords

  • central nervous system
  • heart failure
  • neurons
  • nitric oxide synthase
  • sympathetic nervous system

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Renal Denervation Improves Exaggerated Sympathoexcitation in Rats With Heart Failure : A Role for Neuronal Nitric Oxide Synthase in the Paraventricular Nucleus. / Patel, Kaushik P.; Xu, Bo; Liu, Xuefei; Sharma, Neeru M.; Zheng, Hong.

In: Hypertension, Vol. 68, No. 1, 01.07.2016, p. 175-184.

Research output: Contribution to journalArticle

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