Acute haemodynamic effects of IL-6 treatment in vivo: Involvement of vagus nerve in NO-mediated negative inotropism

Laura Comini, Evasio Pasini, Tiziana Bachetti, Michel Dreano, Gianni Garotta, Roberto Ferrari

Research output: Contribution to journalArticle

Abstract

Interleukin-6 (IL-6) reduces myocardial haemodynamics. However, the intrinsic mechanisms of IL-6 effects are not known. We hypothesized that nitric oxide (NO) synthesised by neuronal synthase (nNOS) can be the molecular mediator of IL-6-mediated cardiac effects. Thus, we investigated in vivo after IL-6 acute administration: (1) the role of NO pathway; (2) the importance of NO derived from nNOS located in intracardiac vagal ganglion in the anterior surface of the left ventricle. Sprague-Dawley (SD) rats (225-250 g) were anaesthetized (sodium pentobarbital 30 mg/kg intraperitoneally administered) and ventilated. The effects of a single IL-6 bolus (100 μg/kg intravenously administered) were studied in four experimental groups: (a) IL-6 (n = 6), (b) IL-6 plus 30 mg/kg of l-NAME (an eNOS and nNOS inhibitor; n = 6), (c) IL-6 plus 25 mg/kg of 7-NI (a specific nNOS inhibitor; n = 6), (d) IL-6 plus vagal resection (n = 6). We evaluated the following parameters: mean aortic pressure (MAP), left ventricular end systolic pressure (LVESP), left ventricular positive peak dP/dt (PP dP/dt). Data are expressed as mean ± sem. IL-6 caused a transient but significant reduction of MAP (-21.8% of basal: p <0.05), LVESP (from 130 ± 4.2 to 1056.5 mmHg: p <0.05) and PP dP/dt (from 5390 ± 158 to 4400 ± 223 mmHg/s, p <0.02). Concomitant treatment with l-NAME or 7-NI totally abolished IL-6 effects. Vagal resection significantly reduced the haemodynamic effects (MAP: -10% of basal: p = ns; LVEDS: from 125 ± 7.3 to 117 ± 6.8 mmHg, p <0.05; PP dP/dt from 5500 ± 150 to 5000 ± 143 mmHg/s, p <0.05). We conclude that acute administration of IL-6 caused transient but significant cardiac negative inotropism. IL-6 haemodynamic effects are partly due to NO synthesised by nNOS located in vagal left ventricular ganglia.

Original languageEnglish
Pages (from-to)236-242
Number of pages7
JournalCytokine
Volume30
Issue number5
DOIs
Publication statusPublished - Jun 7 2005

Keywords

  • Haemodynamics
  • Interleukin-6
  • Nitric oxide
  • Vagus nerve

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Immunology
  • Immunology and Allergy

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