Most Likely Cure To Coronavirus Seems To Revolve Around Angiotensin

[yoshiesque]

I think we all need to start discussing ACE2/Angiotensin/Serotonin, in relation to COVID-19.

See Rays response below. But he has discussed (and studies are out there to show it too) that ACE2 blockers can help a lot. ACE2 I believe is another name for Angiotensin II. I want to understand exactly how this all works. Anyone an expert in this area? I also want to know how it relates to Serotonin. I am hearing mixed things. Some say its important to have ACE2 to combat the virus some say its important to inhibit it.

Kids are barely being affected and its apperently to do with low ACE2 (i think) and it increases with age/health issues. Rays latest interview, he discusses it briefly but I still don't understand how this all works. Who here can chime in? Thank you!

Ray:
The virus uses ACE2 (angiotensin converting enzyme 2) as receptor and enters cells by the angiotensin receptor. Losartan (recommended in China), an angiotensin blocker, is effective protection, and has many other antiinflammatory effects. The Chinese also have good results with cinanserin, a serotonin blocker. I think cyproheptadine might help, too. Progesterone lowers the angiotensin receptor, but doesn’t act immediately as losartan does.

 

[jb116]

No we don't want to block ace2. There's too much confusion on this. Ray is not saying block it either. Blocking angiotensin receptor is a different story. Young people have high ace2

 

[yoshiesque]

Update... I now understand it better. ACE1 promotes angiotensin 2 and ACE2 blocks. Angiotensin 2. The virus binds to ACE2 which means angiotensin 2 will increase excessively. That's why losartan is good. It decreases angiotensin 2. The problem is angiotensin 2 not being able to be removed due. To. ace2

Also.. Seems like it's the angiotensin that kills ppl not the coronavirus itself directly

 

[schultz]

I think the angiotensin system stimulates other inflammatory systems. It's not clear to me if it is the angiotensin system itself causing problems directly or if it is the other systems (or a combination). Nitric oxide for example. Some publications suggest NO is protective against the angiotensin system, but I have a feeling NO is actually one of the main causes of the damage. But I'll have to read more to have it make sense in my brain. The safe answer would be it comes down to balance between the systems.

Edit: Of course I am stuck on the idea that NO is one of the main problems here, so I will probably argue that to the bitter end lol. Just thought I would admit that 'out loud'.

 

[md_a]

…

On the other hand, the most common complication leading to the CoV-induced mortality is respiratory failure due to an extensive, accelerating lung fibrogenesis. Rather than PCRbased testing to detect CoV infection, a radiologic lung infiltration pattern in chest X ray could have a diagnostic value to screen the suspicious patients (7,8). It seems the cytopathic effects of virus resulted from its massive replication in infected cells need more time than what happens to cause acute manifestation of the disease. So, the acute accelerating lung fibrosis induced by COVID19 infection can be justified through ACE-AngII-AT1 overactivation caused by the virus (8). Losartan is an AT1 antagonist with a selective, competitive function which decreases the end organ responses to AngII. It is a common anti-hypertensive agent which is currently prescribed for high blood pressure patients, particularly those who are prone to diabetic nephropathies (9).

…

Accordingly, losartan as a selective antagonist of AT1 receptor which exerts an inhibitory effect on ACE-AngII-AT1 axis in the RAS system, as a known molecular pathway for endorgan fibrosis, may be suggested as a potential agent to protect of lung damage induced by coronavirus. Meanwhile, losartan may lead to protection of lung fibrosis through other molecular mechanisms such as dawnregulation of TGF-β1. This hypothesis need to verify through more in-vitro and in-vivo investigations.

https://www.cambridge.org/core/serv...n_against_coronavirus_induced_lung_damage.pdf

 

[md_a]

...the angiotensin converting enzyme is one of the early parts of our immune system that sets up an inflammatory reaction that will set in action a whole chain of events, if the pathogen gets trough and is actually a treat, then you activate this proteolytic protein that create angiotensin witch is like a transmitter of a panic reaction to the organism, and it happens this coronavirus is able to bind to one of this angiotensin converting enzymes, there is one with is only pro-inflammatory and the other one that backs that up, which undoes, inhibits the inflammatory damage done by the first angiotensin producing enzyme, this is called ACE2, and ACE2 happens to be attacked by this particular virus witch binds to that enzyme, and that’s receptor its vulnerable point of organism as far this fire is concern, and binding to that ACE2 means that it leaves the ACE1 which produces angiotensin, it leaves that free to act, and ACE2 is capable in inactivating angiotensin breaking down to the first seven amino acids, they call it angiotensin 1-7, and this is a defensive anti-inflammatory peptide, so if your ACE2 is knocked out, angiotensin has a free range to cause damage, so the virus increases the inflammatory reaction by sticking to the defensive enzyme, and that enzyme combined with the virus, than acts to enter the cell by way of the angiotensin receptor which is called the AT1, that are two known receptors by which angiotensin can do damage. Angiotensin 1 is strictly an inflammation producing system, the angiotensin 2 produces somewhat defensive reactions, but it happens that the virus enzyme combination entering the cell by way of angiotensin receptor 1, AT1, and that turns on a whole range of destructive processes, nitric oxide, serotonin for example. And, so, just looking at the effects, its obvious you can defend by anything that defends you against nitric oxide and serotonin, so anti-inflammatory things are the known treatment for this kind of virus that Chinese for years have been using, cinanserin which is a serotonin blocker for other treatments, and they find that is helpful for people with the established respiratory corona infection, and losartan witch is high blood pressure drug is the most well-known blocker of angiotensin 1 receptor.. losartan is cheap and widely available. - Ray Peat

 

[md_a]

Duane says:
19 March, 2020 at 8:32 am
This is a disease that is more severe and deadly in the aged, hypertensive, and diabetic. Two consistent findings in these three groups are decreased expression of ACE2, and increased expression of AT-1 receptors compared to the young. If young people have higher ACE2, and that was the factor allowing faster viral innoculation, then it would be worse in the young, but it is not. Aging, diabetes, hypertension, COPD are all conditions that are associated with higher levels of the AT-1 receptor, with greater age or severity related to higher levels. Tissues also react to hypoxia by upregulating AT-1 receptors, and there are more AT-1 receptors on activated lymphocytes. Note the pattern consistent with this disease. Immune competence is less of a factor in this disease as evidenced by the fact that it spares the young almost completely.

In patients with predisposed ACE2/ACE1 imbalance, the viral attachment and internalization of ACE2 increases stimulation of the larger population of AT-1 receptors within the local tissue eliciting further edema, leading to hypoxia, increase AT-1 receptors, etc. I will be interested in the results of the Losartan study.
Angiotensin and the Coronavirus

 

[GenericName86]

Would cyproheptadine be a decent substitute to Losartan? In Aus you need a prescription for it but can get cyproheptadine over the counter. Also how would one get higher ACE2 if it's low?

 

[Ami]

Would cyproheptadine be a decent substitute to Losartan? In Aus you need a prescription for it but can get cyproheptadine over the counter. Also how would one get higher ACE2 if it's low?

No. Ray says (from post above) "...anti-inflammatory things are the known treatment for this kind of virus that Chinese for years have been using, cinanserin which is a serotonin blocker for other treatments, and they find that is helpful for people with the established respiratory corona infection, and losartan witch is high blood pressure drug is the most well-known blocker of angiotensin 1 receptor.. losartan is cheap and widely available.
He also said that cyproheptadine can probably be substituted for cinanserin.

 

[LeeLemonoil]

http://cdn.shopify.com/s/files/1/00...vby5kZSIsICJrbF9jb21wYW55X2lkIjogIkx4Zm1LWCJ9

BACKGROUND: SARS-CoV-2 has caused a series of COVID-19 globally. SARS-CoV-2 binds angiotensin I converting enzyme 2 (ACE2) of renin-angiotensin system (RAS) and causes prevalent hypokalemia METHODS: The patients with COVID-19 were classified into severe hypokalemia, hypokalemia, and normokalemia group. The study aimed to determine the relationship between hypokalemia and clinical features, the underlying causes and clinical implications of hypokalemia. RESULTS: By Feb 15, 2020, 175 patients with COVID-19 (92 women and 83 men; median age, 46 [IQR, 34-54] years) were admitted to hospital in Wenzhou, China, consisting 39 severe hypokalemia-, 69 hypokalemia-, and 67 normokalemia patients. Gastrointestinal symptoms were not associated with hypokalemia among 108 hypokalemia patients (P>0.05). Body temperature, CK, CK-MB, LDH, and CRP were significantly associated with the severity of hypokalemia (P<0.01). 93% of severe and critically ill patients had hypokalemia which was most common among elevated CK, CK-MB, LDH, and CRP. Urine K+ loss was the primary cause of hypokalemia. severe hypokalemia patients was given 3 g/day, adding up to an average of 34 (SD=4) g potassium during hospital stay. The exciting finding was that patients responded well to K+ supplements when they were inclined to recovery. CONCLUSIONS: Hypokalemia is prevailing in patients with COVID-19. The correction of hypokalemia is challenging because of continuous renal K+ loss resulting from the degradation of ACE2. The end of urine K+ loss indicates a good prognosis and may be a reliable, in-time, and
ABOUT | SUBMIT
# Previous
Posted February 29, 2020.
% Download PDF & Data/Code
Tweet Like 2K
| ALERTS / RSS
!
Advanced Search
' Email
( Share
) Citation Tools
Next $
Abstract
COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv
Subject Area
Infectious Diseases (except HIV/AIDS)
Subject Areas
All Articles
Addiction Medicine
Allergy and Immunology
Anesthesia
Cardiovascular Medicine
Dentistry and Oral Medicine
Dermatology
Emergency Medicine
Endocrinology (including Diabetes Mellitus and Metabolic Disease)
Epidemiology
Forensic Medicine Gastroenterology
Genetic and Genomic Medicine Geriatric Medicine
Health Economics
Health Informatics
Health Policy
Hypokalemia and Clinical Implications in Patients with Coronavirus Disease 2019 (COVID-19) Page 1 of 4
Hypokalemia and Clinical Implications in Patients with Coronavirus Disease 2019 (COVID-19) | medRxiv 3/19/20, 9:00 AM
sensitive biomarker directly reflecting the end of adverse effect on RAS system.

 

[md_a]

In Italy “… he noted, 99% of people who died from the virus had an underlying condition, and 75% of them had hypertension.”

As I read this study I wonder if people die of coronavirus following the treatment, using ACE inhibitors by reducing angiotensin 2 in the body.


Cancer, inflammation and the AT1 and AT2 receptors

With regard to cancer being a systemic disease, an examination of supporting evidence for a systemic role of AT1 in relationship to inflammation in disease and injury is presented as a logical progression.

…

In consideration of cancer induced immune suppression, it is further postulated that the inflammation associated with bacterial and viral infections, is also an evolved means of immune suppression by these pathogens and that the damage caused, although incidental, leads to the symptoms of disease and, in some cases, death.

It is anticipated that manipulation of the angiotensin system with existing anti-hypertensive drugs could provide a new approach to the treatment of many of the diseases that afflict mankind.

…

AT1 receptors are expressed in various parts of the body and are associated with their respective functions, such as blood vessels, adrenal cortex, liver, kidney and brain, while AT2 receptors are highest in fetal mesenchymal tissue, adrenal medulla, uterus and ovarian follicles

….

In addition to the mediators reviewed by Suzuki et al (2003) [16], a number of vital molecules in inflammatory processes are induced by the AT1 receptor. These include interleukin-1 beta (IL-1b) in activated monocytes [17], Tumour Necrosis Factor-alpha (TNF-α) [18], Plasminogen Activator Inhibitor Type 1 (PAI-1) [19] and adrenomedullin [20] all of which have been shown to have active participation in various aspects of cancer development. Activation of AT1 also causes the expression of TGF-β [21, 22] and a review of literature indicates this may be a unique capability for this receptor. TGF-β is a multifunctional cytokine that is produced by numerous types of tumours and amongst its many functions is the ability to promote angiogenesis, tissue invasion, metastasis and immune suppression.

….

On examination of the tumour environment, it is interesting to note that angiotensin II actually increases vasodilation, a phenomenon that researchers have attempted to utilise for drug delivery [25]. This would imply something unusual about the presentation of angiotensin receptors; however it is predominantly over expression of the vasoconstrictor AT1 that is reported in association with human cancers of the breast [26], pancreas [27], kidney [28], squamous cell carcinoma [29], keratoacanthoma [29], larynx [30], adrenal gland [30], and lung [31]. AT2 has been identified as expressed in preference to AT1 in only one case, in an earlier paper on colorectal cancer.

…


Hypoxia has been demonstrated to induce the expression of both AT1b (AT1a and AT1b are subsets of AT1) and AT2 receptors in the rat carotid body and pancreas [39, 40]. The expression of AT1 and AT2 receptors has been studied during the development and regression of hypoxic pulmonary hypertension [41]. Hypoxia has been shown to strongly induce the expression of AT1b but not AT1a. The expression of AT2 is believed to protect the cell from apoptosis and this effect has been demonstrated in the brain when AT1 is antagonized [42]. Since HIF-1α governs many hypoxia driven transcriptions [43], its control of AT1b and AT2 expression can be hypothesized. AT1 activation has also been shown to increase the activity of HIF-1α [43], and is consistent with other cases of AT1 providing a positive feedback mechanism. Since hypoxia counts for the expression of AT1b, the speculation that the AT1a subtype is induced by oxidative stress is tempting, although a review of literature appears absent in this regard and further investigation is required to confirm this hypothesis.

….


Tumour progression has been significantly slowed with AT1 receptor antagonists

…

Similarly, the AT1 blocker losartan has been shown to antagonise platelets, which are thought to modulate cell plasticity and angiogenesis via the vascular endothelial growth factor (VEGF) [56]. It has been postulated that losartan and other AT1 blockers can act as novel anti-angiogenic, anti-invasive and anti-growth agents against neoplastic tissue [56].

…

The controlling role of AT receptors in inflammation and healing

Significant evidence has been shown that AT1 receptors are upregulated during disease and that AT2 receptor expression follows behind AT1 expression during injury and healing. Given the opposing roles of AT1 and AT2 it can thus be postulated that the interplay of these receptors plays a significant part in judging the current local status of appropriate versus inappropriate inflammation and in providing feedback to the rest of the body. Indeed it is anticipated that prolonged expression of AT1 combined with a lack of AT2 expression results in sustained chronic inflammation and fibrosis.

….

Given the involvement of AT1 in the immunosuppression and inflammatory processes, as well as in the expression of the pro-inflammatory cytokines and chemokines, it becomes evident that the AT1 receptor is essential for tumour protection and progression. A combination therapy consisting of AT1 receptor antagonists, NSAID for further control of the inflammation and immune therapy in the form of tumour vaccines should provide a novel and successful treatment for solid tumours.

…

From a review of the current disease literature, it has been demonstrated that the role of AT1 and AT2 in inflammation is not limited to cancer-associated inflammation, but is generally consistent and system wide. Potential therapy by manipulation of these receptors, although at an early stage, has been demonstrated for some of these diseases and it is proposed that this approach will provide an effective basis for the treatment of autoimmune, inflammatory and neurodegenerative disorders using existing drugs. AT1 receptor blockade should, in addition, provide a treatment to alleviate the damage caused by bacterial and viral infections, where their destructive action is through chronic inflammation. Given the importance of the immune suppressant effect of inflammation in cancer, it is anticipated that AT1 blockade should also serve to elicit a more effective immune response to other invaders that seek to corrupt the wound recovery process.


Manipulation of the AT1 and AT2 receptors has profound and exciting implications in the control of disease.

Cancer, inflammation and the AT1 and AT2 receptors | Journal of Inflammation | Full Text