Blood pressure regulation by endocannabinoids and their receptors

Abstract

Cannabinoids and their endogenous and synthetic analogs exert powerful hypotensive and cardiodepressor effects by complex mechanisms involving direct and indirect effects on myocardium and vasculature. On the one hand, endocannabinoids and cannabinoid receptors have been implicated in the hypotensive state associated with hemorrhagic, endotoxic and cardiogenic shock, and advanced liver cirrhosis. On the other hand, there is emerging evidence suggesting that the endocannabinergic system plays an important role in the cardiovascular regulation in hypertension. This review is aimed to discuss the in vivo hypotensive and cardiodepressant effects of cannabinoids mediated by cannabinoid and TRPV 1 receptors, and focuses on the novel therapeutical strategies offered by targeting the endocannabinoid system in the treatment of hypertension.

Association of polymorphisms in the endocannabinoid system genes with myocardial infarction and plasma cholesterol levels

“…Considering the lack of blood pressure lowering action of anandamide in mice lacking CB1 receptors, polymorphism in the human CB1 receptor gene also might be expected to shift tonic levels of these compounds. The present study reports no case-control differences either in genotype distributions or allelic frequencies of the CB1 polymorphism in association to heart failure 26 . There is growing evidence that genetic variation in CNR1 directly influences metabolic traits in humans by altering the activity of CB1 receptor dependent signalling in peripheral tissues.…”

Activation of endocannabinoid system is associated with persistent inflammation in human aortic aneurysm

“…Therefore, examination of suitable genetically or pharmacologically engineered animal models without dissection should be performed in future studies. Endocannabinoids have been associated in experimental studies with arterial pressure regulation, which by now did not yield a specific pharmacological target [27], whereas its association in metabolic homeostasis and diabetes development offers some promising cues [28]. Despite effects on hypertension or diabetes and inability to clearly delineate them from other pathologies, the short action of endocannabinoids due to their fast degradation makes us confident to claim the observed results as representative for the endocannabinoid level in the aortic wall.…”

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

“…CB 1 receptors have been detected in the human, rat, and mouse myocardium where they mediate negative inotropy (Bonz et al, 2003;Bá tkai et al, 2004b;Pacher et al, 2004bPacher et al, , 2005aEngeli et al, 2005;Wagner et al, 2005) and also in vascular tissues (Gebremedhin et al, 1999;, where their activation leads to vasodilation, and both of these effects appear to be involved in the hypotensive effect of anandamide (Wagner et al, 2001a,b;Bá tkai et al, 2004a,b;Pacher et al, 2004bPacher et al, , 2005a in anesthetized rodents. Sympathetic nerve terminals contain presynaptic CB 1 receptors, stimulation of which inhibits norepinephrine release (Ishac et al, 1996), which contributes to the bradycardic effects of anandamide in vivo (Wagner et al, 2001b).…”