The interaction between the endocannabinoid system and the renin angiotensin system and its potential implication for COVID-19 infection

Abstract

Background: Coronavirus disease 2019 (COVID-19) is spreading fast all around the world with more than fourteen millions of detected infected cases and more than 600.000 deaths by 20th July 2020. While scientist are working to find a vaccine, current epidemiological data shows that the most common comorbidities for patients with the worst prognosis, hypertension and diabetes, are often treated with angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). Body: Both ACE inhibitors and ARBs induce overexpression of the angiotensin converting enzyme 2 (ACE-2) receptor, which has been identified as the main receptor used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter into the alveolar cells of the lungs. While cannabinoids are known to reduce hypertension, the studies testing the hypotensive effects of cannabinoids never addressed their effects on ACE-2 receptors. However, some studies have linked the endocannabinoid system (ECS) with the renin angiotensin system (RAS), including a cross-modulation between the cannabinoid receptor 1 (CB1) and angiotensin II levels. Conclusion: Since there are around 192 million people using cannabis worldwide, we believe that the mechanism underlying the hypotensive properties of cannabinoids should be urgently studied to understand if they can also lead to ACE-2 overexpression as other antihypertensive drugs do.

Prediction of Breast Cancer Risk Factors Using Neural Network Analytics: an Empirical Study

“…Platelet production would be also promoted by Ang 1-7 [31]. Since MLT may also promote lymphocyte and platelet generation this evidence would furtherly confirm the connection occurring between MLT and Ang 1-7 [5,15].…”

“…In addition to their effects on endothelial characteristics, Ang II and Ang 1-7 may also influence the hematopoietic activity, then cell content of blood. As well as for their cardiovascular effects, Ang II and Ang 1-7 would play opposite effects on hematopoietic differentiation and immune cells function [15][16][17][18][19]. Even though the results are still preliminary, it seems that Ang 1-7 may promote lymphocyte differentiation, and inhibit monocyte generation and macrophage system activation.…”

“…Even though the complex molecular mechanisms need to be better investigated and defined, it has been shown that Ang II plays a major procoagulant action by inducing an endothelial damage, whereas Ang 1-7 has appeared to exert a clear anti-thrombotic activity with a following potential therapeutic efficacy also in the treatment of Covid19 disease since the thromboembolic events may represent one of the major causes of death in association with respiratory distress-induced lung failure [15][16][17][18][19]32]. In fact, according to the recent discoveries, would constitute a disease consisting of an acute and severe Ang 1-7 deficiency [32].…”

“…Not only, but the investigation of endothelial cells would have at least to include the mechanisms responsible for the neo-angiogenic function, their coagulation properties, and their fibrotic processes. By summarizing , the most important endogenous molecules involved in the inhibition of endothelialrelated inflammation are represented by the pineal hormones, such as melatonin (MLT), which is the most studied pineal hormone the endogenous cannabinoids ang And 1-7 [4,15,16,[9][10][11][12].…”

In quest of a new therapeutic approach in COVID-19: the endocannabinoid system

“…As stated before, the angiotensin-converting enzyme (ACE) receptor is the main receptor in the pathophysiology for the SARS-CoV-2 (Sainz-Cort and Heeroma 2020 ). Despite the lack of experimental studies, the hypotensive effect of cannabinoids could be explained by their agonist effect on the ACE receptor (Sainz-Cort and Heeroma 2020 ). Another paper pointed out that some Cannabis sativa lines could downregulate the expression of ACE-2 (Wang et al.…”