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. SpragueeDawley (SD) rats (225e250 g) were anaesthetized (sodium pentobarbital 30 mg/kg intraperitoneally administered) and ventilated. The effects of a single IL-6 bolus (100 mg/kg intravenously administered) were studied in four experimental groups: (a) IL-6 (nZ6), (b) IL-6 plus 30 mg/kg of L-NAME (an eNOS and nNOS inhibitor; nZ6), (c) IL-6 plus 25 mg/kg of 7-NI (a specific nNOS inhibitor; nZ6), (d) IL-6 plus vagal resection (nZ6). 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 meanGsem. IL-6 caused a transient but significant reduction of MAP (21.8% of basal: p!0.05), LVESP (from 130G4.2 to 1056.5 mmHg: p!0.05) and PP dP/dt (from 5390G158 to 4400G223 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: pZns; LVEDS: from 125G7.3 to 117G6.8 mmHg, p!0.05; PP dP/dt from 5500G150 to 5000G143 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. 2005 Elsevier Ltd. All rights reserved.

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

FERRARI, Roberto
2005

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. SpragueeDawley (SD) rats (225e250 g) were anaesthetized (sodium pentobarbital 30 mg/kg intraperitoneally administered) and ventilated. The effects of a single IL-6 bolus (100 mg/kg intravenously administered) were studied in four experimental groups: (a) IL-6 (nZ6), (b) IL-6 plus 30 mg/kg of L-NAME (an eNOS and nNOS inhibitor; nZ6), (c) IL-6 plus 25 mg/kg of 7-NI (a specific nNOS inhibitor; nZ6), (d) IL-6 plus vagal resection (nZ6). 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 meanGsem. IL-6 caused a transient but significant reduction of MAP (21.8% of basal: p!0.05), LVESP (from 130G4.2 to 1056.5 mmHg: p!0.05) and PP dP/dt (from 5390G158 to 4400G223 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: pZns; LVEDS: from 125G7.3 to 117G6.8 mmHg, p!0.05; PP dP/dt from 5500G150 to 5000G143 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. 2005 Elsevier Ltd. All rights reserved.
2005
Comini, L; Pasini, E; Bachetti, T; Dreano, M; Garotta, G; Ferrari, Roberto
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1202708
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