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by snapetom 2295 days ago
> ACE inhibitors (lisinopril, etc.) are generally though to be enzymatic inhibitors of ACE, not ACE2

Correct. Ace inhibitors have shown no effect on ACE2.

https://www.nrcresearchpress.com/doi/10.1139/y02-021

1 comments

Some more recent research seem to at least partially contradict this statement and seem to suggest ACE inhibitors do affect ACE2.

https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1440-1681....

https://www.ncbi.nlm.nih.gov/pubmed/15897343

In addition there is also this specific recent Covid19 paper which does cautiously attract attention on this matter.

https://www.nature.com/articles/s41569-020-0360-5

I had a talk with 2 cardiologists and their response (this is not medical advice, talk to your cardiologist) was that it would be reasonable at least until further research is completed to for instance switch medication from ACE inhibitors to a Calcium Channel Blocker (such as Lercanidipine). At least until the pandemic gets under control and/or vaccine/treatment is available and validated.

There are very few cons to this safety measure if this can prevent complications. But that's my sole opinion and again, not medical advice. This might be worth at least an inquiry to your cardiologist. Especially if you're over 60.

(Sorry for by bad English, not a native speaker)

Your English is fine.

However, your first two papers seem to state ACE inhibitors makes ACE2 worse in terms of COVID-19.

"Losartan increased plasma levels of both Ang II and Ang-(1-7), as well as cardiac ACE2 mRNA and cardiac ACE2 activity"

The last one does nothing except say, "someone should look at it."

I am a native English speaker, and your English was literally flawless.
I thought your English was great. Your post is perfectly readable. :)
Your english is fine! Better than mine and I have been a native speaker for 32 years!
upregulation of ACE2 means the mRNA that is responsible for the code to make ACE2 protien is being transcribed.

this does not mean the ACE2 enzyme activity or concentration is increased

So, looking at the NIH conclusion, if I'm on a *saratan and read this:

"Selective blockade of either Ang II synthesis or activity induced increases in cardiac ACE2 gene expression and cardiac ACE2 activity, whereas the combination of losartan and lisinopril was associated with elevated cardiac ACE2 activity"

should I check in with my cardiologist?

first off drugs that influence the components of the RAS are not childs play, so yes consult your doctor[s] rather than experimenting with dosages.

This is only just starting to see clinical trials, meaning the people involved are under direct physician supervision.

regarding ACE2:

this increased production of ACE2 is an indirect effect of ACE2 disruption.

you have to be careful with these sorts of experiments. when you block angiotensin II receptors that means there is a reduction of signal for angiotensin II being present.

This angiotensin that would ordinarily be interacting with the ATreceptors is now available for ACE2 to operate upon.

the summary here is that increased enzymatic product doesnt mean the enzyme has been "turbocharged" . If there is an increased ratio of reactants to products this will cause increased concentration of products in total but does not change the intrinsic rate at which the enzyme actually operates.

This looks like a case of substrate concentration dependent equilibrium driving reaction rate.

Thank you very much for the info and taking a look at it!
basically ACE2 is a regulator that converts between angiotensin II <--> angiotensin 1,7

these have opposite effects , angiotensin II is a vaso-constrictor, thus increases blood pressure.

angoitensin 1,7 is a vaso-dialator, thus decreases blood pressure. so there is an equilibrium state of the two established by ACE2. this is something that ACE inhibitors or ARB blockers dont directly influence.