Differential Sympathetic Vasomotor Activation Induced by Liver Cirrhosis in Rats

PLoS One. 2016 Apr 7;11(4):e0152512. doi: 10.1371/journal.pone.0152512. eCollection 2016.

Abstract

We tested the hypothesis that there is a topographical sympathetic activation in rats submitted to experimental cirrhosis. Baseline renal (rSNA) and splanchnic (sSNA) sympathetic nerve activities were evaluated in anesthetized rats. In addition, we evaluated main arterial pressure (MAP), heart rate (HR), and baroreceptor reflex sensitivity (BRS). Cirrhotic Wistar rats were obtained by bile duct ligation (BDL). MAP and HR were measured in conscious rats, and cardiac BRS was assessed by changes in blood pressure induced by increasing doses of phenylephrine or sodium nitroprusside. The BRS and baseline for the control of sSNA and rSNA were also evaluated in urethane-anesthetized rats. Cirrhotic rats had increased baseline sSNA (BDL, 102 vs control, 58 spikes/s; p<0.05), but no baseline changes in the rSNA compared to controls. These data were accompanied by increased splanchnic BRS (p<0.05) and decreased cardiac (p<0.05) and renal BRS (p<0.05). Furthermore, BDL rats had reduced basal MAP (BDL, 93 vs control, 101 mmHg; p<0.05) accompanied by increased HR (BDL, 378 vs control, 356; p<0.05). Our data have shown topographical sympathetic activation in rats submitted to experimental cirrhosis. The BDL group had increased baseline sSNA, independent of dysfunction in the BRS and no changes in baseline rSNA. However, an impairment of rSNA and HR control by arterial baroreceptor was noted. We suggest that arterial baroreceptor impairment of rSNA and HR is an early marker of cardiovascular dysfunction related to liver cirrhosis and probably a major mechanism leading to sympathoexcitation in decompensated phase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Baroreflex*
  • Blood Pressure*
  • Cardiovascular Diseases / physiopathology
  • Disease Models, Animal
  • Heart Rate*
  • Liver Cirrhosis / physiopathology*
  • Male
  • Rats
  • Rats, Wistar
  • Splanchnic Nerves / physiopathology*
  • Vasomotor System / physiopathology*

Grants and funding

This study was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) 2013/22522-9 and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) 472613/2013-8 and 301840/2013-0. Heder F. G. Estrela was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.