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 language | English |
|---|---|
| Pages (from-to) | 236-242 |
| Number of pages | 7 |
| Journal | Cytokine |
| Volume | 30 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Jun 7 2005 |
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Keywords
- Haemodynamics
- Interleukin-6
- Nitric oxide
- Vagus nerve
ASJC Scopus subject areas
- Endocrinology
- Molecular Biology
- Immunology
- Immunology and Allergy
Cite this
Acute haemodynamic effects of IL-6 treatment in vivo : Involvement of vagus nerve in NO-mediated negative inotropism. / Comini, Laura; Pasini, Evasio; Bachetti, Tiziana; Dreano, Michel; Garotta, Gianni; Ferrari, Roberto.
In: Cytokine, Vol. 30, No. 5, 07.06.2005, p. 236-242.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Acute haemodynamic effects of IL-6 treatment in vivo
T2 - Involvement of vagus nerve in NO-mediated negative inotropism
AU - Comini, Laura
AU - Pasini, Evasio
AU - Bachetti, Tiziana
AU - Dreano, Michel
AU - Garotta, Gianni
AU - Ferrari, Roberto
PY - 2005/6/7
Y1 - 2005/6/7
N2 - 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.
AB - 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.
KW - Haemodynamics
KW - Interleukin-6
KW - Nitric oxide
KW - Vagus nerve
UR - http://www.scopus.com/inward/record.url?scp=20144363219&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20144363219&partnerID=8YFLogxK
U2 - 10.1016/j.cyto.2005.01.009
DO - 10.1016/j.cyto.2005.01.009
M3 - Article
VL - 30
SP - 236
EP - 242
JO - Cytokine
JF - Cytokine
SN - 1043-4666
IS - 5
ER -