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

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.