Novel mechanisms of sympathetic regulation in chronic heart failure

Research output: Contribution to journalShort surveypeer-review

136 Scopus citations

Abstract

Until recently, the mechanisms by which sympathetic activation occurs in the CHF state have been largely unknown, and therapy targeting the sympathetic nervous system and the renin-angiotensin system has been more empirical than evidence based. With the advent of newer techniques to localize and evaluate the function of the central renin-angiotensin system in normal and disease states, a picture is emerging that implicates Ang II and its receptors as a pivotal regulator of sympathetic function by virtue of its role in the generation of oxidative stress and the regulation of membrane ion channel function. One of the most important and reproducible aspects of the role of Ang II in CHF relates to the modulation of the AT1 receptor. A novel pathway that has come from this work is the upregulation of the AT1 receptor in the face of elevated levels of Ang II. This seems to be mediated by activation of the transcription factor AP1 through a cJun/Jnk pathway. The increase in central oxidative stress seems to play a major role in activation of sympathetic outflow in CHF. Superoxide anion production along with a reduction in SOD protein and activity may contribute to either activation or sensitization of specific populations of neurons through alterations in both potassium and calcium channel activity. In addition, reductions in the sympathoinhibitory influence of NO because of both increased scavenging of NO and a reduction in nNOS activity in the CHF state contribute to sympathoexcitation. Figure 4 provides a schematic overview of the relevant central events and pathways that may impact sympathetic nerve activity in the CHF state and the effects of exercise training.

Original languageEnglish (US)
Pages (from-to)1005-1011
Number of pages7
JournalHypertension
Volume48
Issue number6
DOIs
StatePublished - Dec 2006

ASJC Scopus subject areas

  • Internal Medicine

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