Presynaptic cannabinoid CB1 receptors are involved in the inhibition of the neurogenic vasopressor response during septic shock in pithed rats
Article first published online: 29 JAN 2009
2004 British Pharmacological Society
British Journal of Pharmacology
Volume 142, Issue 4, pages 701–708, June 2004
How to Cite
Godlewski, G., Malinowska, B. and Schlicker, E. (2004), Presynaptic cannabinoid CB1 receptors are involved in the inhibition of the neurogenic vasopressor response during septic shock in pithed rats. British Journal of Pharmacology, 142: 701–708. doi: 10.1038/sj.bjp.0705839
- Issue published online: 29 JAN 2009
- Article first published online: 29 JAN 2009
- (Received December 19, 2003, Revised April 10, 2004, Accepted April 14, 2004)
- Presynaptic inhibition;
- septic shock;
- cannabinoid CB1 receptor;
- cannabinoid CB2 receptor;
- SR 141716A;
- vanilloid VR1 receptor;
- histamine H3 receptor;
- pithed rat
Our study was undertaken to investigate whether bacterial endotoxin/lipopolysaccharide (LPS) affects the neurogenic vasopressor response in rats in vivo by presynaptic mechanisms and, if so, to characterize the type of presynaptic receptor(s) operating in the initial phase of septic shock.
In pithed and vagotomized rats treated with pancuronium, electrical stimulation (ES) (1 Hz, 1 ms, 50 V for 10 s) of the preganglionic sympathetic nerve fibers or intravenous bolus injection of noradrenaline (NA) (1–3 nmol kg−1) increased the diastolic blood pressure (DBP) by about 30 mmHg. Administration of LPS (0.4 and 4 mg kg−1) under continuous infusion of vasopressin inhibited the neurogenic vasopressor response by 25 and 50%, respectively. LPS did not affect the increase in DBP induced by exogenous NA.
The LPS-induced inhibition of the neurogenic vasopressor response was counteracted by the cannabinoid CB1 receptor antagonist SR 141716A (0.1 μmol kg−1), but not by the CB2 receptor antagonist SR 144528 (3 μmol kg−1), the vanilloid VR1 receptor antagonist capsazepine (1 μmol kg−1) or the histamine H3 receptor antagonist clobenpropit (0.1 μmol kg−1). The four antagonists by themselves did not affect the increase in DBP induced by ES or by injection of NA in rats not exposed to LPS.
We conclude that in the initial phase of septic shock, the activation of presynaptic CB1 receptors by endogenously formed cannabinoids contributes to the inhibition of the neurogenic vasopressor response.
British Journal of Pharmacology (2004) 142, 701–708. doi:10.1038/sj.bjp.0705839