Anandamide and endocannabinoid system: an attractive therapeutic approach for cardiovascular disease

Abstract

Cardiovascular disease is currently not adequately managed and has become one of the main causes of morbidity and mortality worldwide. Current therapies are inadequate in terms of preventing its progression. There are several limitations, such as poor oral bioavailability, side effects, low adherence to treatment, and high dosage frequency of formulations due to the short half-life of the active ingredients used, among others. This review aims to highlight the most relevant aspects of the relationship between the cardiovascular system and the endocannabinoid system, with special attention to the possible translational effect of the use of anandamide in cardiovascular health. The deep and detailed knowledge of this interaction, not always beneficial, and that for years has gone unnoticed, is essential for the development of new therapies. We discuss the most recent and representative results obtained in the field of basic research, referring to the aforementioned subject, emphasizing fundamentally the main role of nitric oxide, renal physiology and its deregulation in pathological processes.

The FAAH Inhibitor URB597 Modulates Lipid Mediators in the Brain of Rats with Spontaneous Hypertension

“…FAAH is a membrane-associated enzyme that is responsible for the degradation of endocannabinoids [ 12 ]. Therefore, the endocannabinoid system is an attractive therapeutic target for the treatment of hypertension and other cardiovascular diseases [ 9 , 13 ]. Given that AEA levels have been shown to regulate blood pressure [ 13 ], FAAH inhibitors are thought to be potential antihypertensive agents.…”

“…Therefore, the endocannabinoid system is an attractive therapeutic target for the treatment of hypertension and other cardiovascular diseases [ 9 , 13 ]. Given that AEA levels have been shown to regulate blood pressure [ 13 ], FAAH inhibitors are thought to be potential antihypertensive agents. Previous studies in SHRs demonstrated that acute administration of the FAAH inhibitors URB597 [ 14 ] and AM3506 [ 15 ] results in a normalization of blood pressure and a decrease in cardiac contractility.…”

N‑linoleyltyrosine protects PC12 cells against oxidative damage via autophagy: Possible�involvement of CB1 receptor regulation

“…It has been demonstrated that as the ligand for the cannabinoid type 1 (CB1) and 2 (CB2) receptors, anandamide (AEA) exerts neuroprotective effects by inhibiting oxidative stress and free radical formation ( 8 ). Additionally, cannabinoids and activating cannabinoid receptors induce autophagy in cardiovascular disease ( 9 - 11 ).…”

Effects of Oleamide on the Vasomotor Responses in the Rat

“…For example, they decrease blood pressure (BP) and heart rate in humans, as well as in experimental animals, reduce tissue damage, delay the progression of the lesion, reduce the likelihood of presenting arrhythmias due to acute myocardial infarction, 4,5 and delay the development of atherosclerosis. [6][7][8] On the other hand, it has been shown that activation of CB1 receptors by anandamide produced by macrophages 9 or 2-AG by platelets 10 significantly contributes to the hypotension that occurs in different types of shock. 8,11 However, the mechanisms by which eCBs produce these physiological effects are not yet elucidated.…”

“…[6][7][8] On the other hand, it has been shown that activation of CB1 receptors by anandamide produced by macrophages 9 or 2-AG by platelets 10 significantly contributes to the hypotension that occurs in different types of shock. 8,11 However, the mechanisms by which eCBs produce these physiological effects are not yet elucidated. 12 Oleamide, an amide derived from oleic acid, is considered an eCB that is naturally produced in some animals.…”