by Cannabinoids and endocannabinoid systems may therefore present useful targets for therapy following myocardial infarction. strong class=”kwd-title” Keywords: Cannabinoids, endocannabinoids, myocardial infarction, cardiac remodelling It is widely accepted that there are endocannabinoid systems within the central nervous system (Di Marzo, 1999), but cannabinoid receptors are also found in peripheral tissues, with both CB1 and CB2 receptors being reported in functional and molecular studies of the Ursocholic acid cardiovascular system (see review by Randall em et al /em ., 2002). in the heart and circulation, in a series of studies, Wagner and his co-workers have put forward evidence that this endocannabinoid system might be activated in cardiovascular pathology. They have reported that hypotension is usually reduced by the CB1 receptor antagonist SR 141716A in both haemorrhagic and endotoxic shock and that platelets and monocytes from rats in endotoxic shock can lower blood pressure in normal rats in a way that is sensitive to the cannabinoid antagonist (Wagner em et al /em ., 1998). They also showed that this platelets and monocytes from the rats with shock were generating anandamide and 2-AG. Now, in this issue, Wagner em et al /em . (2003) report an approach to see if exogenous or endogenous cannabinoids can change cardiac remodelling after myocardial infarction. Myocardial ischaemia occurs when the Ursocholic acid coronary circulation is usually impaired. Although reperfusion is the best method to salvage ischaemic myocardium, it is associated with additional damage known as reperfusion injury. Collectively, ischaemia/reperfusion injury (IRI) can, in the short-term, result in one or more of irreversible cellular damage (infarct), reversible contractile dysfunction (stunning) and arrhythmogenesis. In the longer term, mycardial infarction and IRI can trigger a process by which the morphology and size of the heart is usually PPP3CC affected in a process known as remodelling. Current therapies are targeted at limiting remodelling because the process is usually well correlated with mortality and morbidity (Jugdutt, 1993). Despite its importance, other than agents used to enhance reperfusion, there are no treatments currently available specifically to limit the consequences of IRI and myocardial infarction. Although early treatment with angiotensin-converting enzyme inhibitors (ACEI) is effective in reducing the early phase of remodelling, there is still a significant incidence of mortality (Pfeffer em et al /em ., 1997). Therefore, there is a need to develop therapies designed to limit myocardial damage and act as complementary or option treatments to ACEI in the early phases of remodelling. In light of this need, it is interesting to note that a number of recent reports have highlighted a potentially important role for endocannabinoids in modifying the recovery from, or the severity of, IRI. Endocannabinoids may be involved in the mechanisms by which lipopolysaccharide endotoxin limits infarct size (Lagneux & Lamontagne, 2001) and they might limit mortality after coronary artery occlusion (Wagner em et al /em ., 2001). Although the CB1 receptor antagonist SR 141716A increased blood pressure in animals suffering cardiogenic shock after myocardial infarction relative to infarcted animals not given the drug, it increased the mortality rate and enhanced endothelial dysfunction; this suggests that endocannabinoids might be protective in cardiogenic shock (Wagner em et al /em ., 2001). In their latest paper, Wagner em et al /em . (2003) report that early remodelling in a model in which there is no reperfusion after coronary artery occlusion is limited by the nonselective cannabinoid agonist HU-210. Interestingly, the CB1-receptor antagonist, AM-251 had no effect on survival in contrast to Ursocholic acid the effects of the very closely related SR 141716A (Wagner em et al /em ., 2001); the two antagonists differ only in an iodine for chlorine substitution on one phenyl ring. Although caution needs to be exercised in interpretation, as CB1-receptor impartial actions of SR 141716A have been reported when used at higher concentrations (White & Hiley, 1998), this obtaining correlates.
