Some research on Ang II activity with regard to autonomic problems

[MTRJ75]

This is somewhat connected to the saline infustion/oral rehydration articles I recently posted, but focuses on autonomic nerve damage in addition to or instead of low blood volume: 

https://www.healthrising.org/blog/2020/09/28/paradox-chronic-fatigue-syndrome-pots-renin-aldosterone/

My key takeaways: 

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The authors believed that reduced angiotensin levels were probably responsible, but also suggested the damaged autonomic nerves in the kidney could be a factor.

I've asked the neurologist about autonomic dysfunction vs autonomic nerve damage. Is it possible to test for autonomic nerve damage easily or figure out if there's a particular autoimmune/antibody cause? 

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The big news, though, was that instead of having low Ang II levels, the low blood volume and low-flow POTS patients had dramatically increased Ang II levels (2-3 times normal), as well as low renin levels....

High Ang II levels potentially set the stage for a ramped up fight/flight system, narrowed blood vessels, inflammation and possibly reduced blood flows to the brain...

 

High Ang II levels also appear to be responsible for the defects in the vasodilation in the small blood vessels in the skin, which sometimes cause acrocyanosis (bluish color) in the hands and feet.

How is blood volume tested? Ang II levels? 

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They infused Ang II into POTS patients and healthy controls. As suspected ,the healthy controls responded to the increased Ang II with increased blood pressure: the POTS patients, however, did not.

That suggested that Ang II receptors lining the smooth muscles of the blood vessels were simply not responding well in POTS and that the desensitization hypothesis might be correct.

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The findings suggested that the Ang II levels were having various effects: blood pressure was not being regulated normally, and the heart rate appeared to be affected. Sodium retention, though, was fine.

...

The authors speculated that genetic mutations might play a role, but then introduced a strange possibility: they might not be measuring Ang II at all; but might be measuring Ang 3 or 4. Perhaps Ang II levels were normal, but Ang III or IV levels were increased.

In 2018, the same Oklahoma team that uncovered the presence of adrenergic and muscarinic autoantibodies in POTS found autoantibodies to ang II receptors in a small study. They believe these antibodies stimulate Ang II receptor activity and thus increase Ang II levels.

Okay, so any kind of Ang II measurement (or Ang III or Ang IV) wouldn't even mean anything if the receptors were damaged/dysfunctional. So it's really the antibody tests that important, which I'd guess is not something rheumys or any other doctors regularly check for? 

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Treatments help some and not others, and can come with side effects. Remarkably few studies have been done given how often some of the drugs are used in POTS. Possible treatments include:

• Fludrocortisone (Florinef) – an aldosterone enhancer that increases sodium and water retention – Find out more here. (Tried this, didn't work for me - in fact gave me the worst run of PVCs)
• Desmopression (DDAVP, Stimate) – a synthetic analog of arginine vasopressin that increases intravascular volume.
• Erythropoietin – a hormone that increases blood volume.
• Saline Infusions  – increases blood volume – find out more here. (Not a long term option for some.)
• Oral rehydration solution (WHO formula) – increases blood volume – find out how here. (Experimenting with this now.)

Again, though if antibodies are causing nerve damage that's at the root of all this, is there a safe and better way to stop that rather than treating the effects of the problem? 

Of course, it's also entirely possible that I'm misinterpreting much of this and over-simplifying it due to wishful thinking. 

[p8d]

Thank you for posting this. Very interesting research. I recently had my renin, aldosterone and ang II tested. My renin was low but within range for standing and low for supine but they did the test seated so? It’s definitely low either way. Aldosterone was the same, low but within range and angII range is listed as <=52 and mine was 33. I haven’t yet been in contact with the endocrinologist about the results. Strangely, I control my BP with fluid intake so it somehow has to be connected to RAAS and/or baroreflex but I can’t figure it out. I definitely have autoimmune disease (UCTD) and tested positive for alpha a 1 adregenic antibodies through Celltrend. I am on SCIG and have been weaning down on my alpha blocker because after a dose increase of IG and/or stopping gabapentin my BP dropped from hypertensive crisis territory to usually <150/80s and sometimes even to normal but with serious OH of 20-50 points. So it’s certainly possible that the immunoglobulins are helping but I am overdosed on the guanfacine. Does any of this make sense? My brain is definitely still foggy!

[p8d]

This is a bit old https://pubmed.ncbi.nlm.nih.gov/23931777/ but discusses testing of the autonomic nervous system including  QSART which I think tests nerves, I was diagnosed with SFN because of a positive QSART and negative EMG.

[MTRJ75]

3 hours ago, p8d said:

This is a bit old https://pubmed.ncbi.nlm.nih.gov/23931777/ but discusses testing of the autonomic nervous system including  QSART which I think tests nerves, I was diagnosed with SFN because of a positive QSART and negative EMG.

My cardiologist thinks the Tilt Table test often just makes the person feel terrible and confirms what they already know. I've also read about the sweat test and that seems much more trouble than it's worth. Maybe I should talk to my endo rather than neuro about specific bloodwork. Or maybe it's a 24 hour type test for some of this stuff rather than a snapshot? I'd be most interested in getting some testing done during these fall months when I'm feeling my worst. 

[p8d]

I agree with your cardiologist. The TTT was agony as was the EMG but my neuro trained at Mayo and ran all the tests they do. The QSART wasn’t a big deal I don’t think.