Acute haemodynamic effects of IL-6 treatment in vivo: involvement of vagus nerve in NO-mediated negative inotropism.
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 microg/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 25mg/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.
Comini
Laura
L
Cardiovascular Research Centre, Salvatore Maugeri Foundation, IRCCS, Via Pinidolo, 23, 25064 Gussago, Brescia, Italy. lcomini@fsm.it
Pasini
Evasio
E
Bachetti
Tiziana
T
Dreano
Michel
M
Garotta
Gianni
G
Ferrari
Roberto
R
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000294:innervation / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000097:blood*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology*
D004791:Enzyme Inhibitors; D015850:Interleukin-6; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase