Pál Pacher and Sándor Bátkai contributed equally to this work.
Haemodynamic profile and responsiveness to anandamide of TRPV1 receptor knock-out mice
Article first published online: 9 JUL 2004
The Journal of Physiology
Volume 558, Issue 2, pages 647–657, July 2004
How to Cite
Pacher, P., Bátkai, S. and Kunos, G. (2004), Haemodynamic profile and responsiveness to anandamide of TRPV1 receptor knock-out mice. The Journal of Physiology, 558: 647–657. doi: 10.1113/jphysiol.2004.064824
- Issue published online: 9 JUL 2004
- Article first published online: 9 JUL 2004
- (Received 17 March 2004; accepted 29 April 2004; first published online 30 April 2004)
The endocannabinoid anandamide and cannabinoid (CB) receptors have been implicated in the hypotension in various forms of shock and in advanced liver cirrhosis. Anandamide also activates vanilloid TRPV1 receptors on sensory nerve terminals, triggering the release of calcitonin gene-related peptide which elicits vasorelaxation in isolated blood vessels in vitro. However, the contribution of TRPV1 receptors to the in vivo hypotensive effect of anandamide is equivocal. We compared the cardiac performance of anaesthetized TRPV1 knockout (TRPV1−/−) mice and their wild-type (TRPV1+/+) littermates and analysed in detail the haemodynamic effects of anandamide using the Millar pressure–volume conductance catheter system. Baseline cardiovascular parameters and systolic and diastolic function at different preloads were similar in TRPV1−/− and TRPV1+/+ mice. The predominant hypotensive response to bolus intravenous injections of anandamide and the associated decrease in cardiac contractility and total peripheral resistance (TPR) were similar in TRPV1+/+ and TRPV1−/− mice, as was the ability of the CB1 receptor antagonist SR141716 to completely block these effects. In TRPV1+/+ mice, this hypotensive response was preceded by a transient, profound drop in cardiac contractility and heart rate and an increase in TPR, followed by a brief pressor response, effects which were unaffected by SR141716 and were absent in TRPV1−/− mice. These results indicate that mice lacking TRPV1 receptors have a normal cardiovascular profile and their predominant cardiovascular depressor response to anandamide is mediated through CB1 receptors. The role of TRPV1 receptors is limited to the transient activation of the Bezold-Jarisch reflex by very high initial plasma concentrations of anandamide.