Renin & Aldesterone - The Article

[issie]

This is a bump with another finding in regard to angiotension and an experiment that I did. I tried Lorsartan and it didn't work well for me. I wonder if you just had high bp's without the high noriepi's if this would have worked. It lowers angiotension and raises NO (nitric oxide) levels. It also raises your potassium levels. With high bp's my doctor told me not to salt load. I had figured this out on my own - that wasn't good for me.

Just thought some of you new ones might find this interesting.

Issie

[ramakentesh]

Angiotensin II is a pretty confusing substance. It potentiates NE receptor sensitivity and NE release. it potentiates endothelial disfunction and inflammation. Sometimes the anxiety in POTs can be related to hypocapnia and adrenaline as a response to inappropriate circulatory control, although many of us have excessive amounts of NE leaking into our vasculature. Angiotensin II may also have an effect on norepinephrine reuptake and even NET expression.

Time will tell.

Losarten may actually make some POTS patients worse rather than better because it will increase nitric oxide activation which maybe an issue in a large subset of patients.

[Annaliese]

Issie. I loooove that youre bringing up this renin aldosterone issue. Thank you.

[issie]

Annaliese,

Glad you liked it. This was done a while back, but I still feel that there is a connection. Sorry your doc wouldn't test you. Of all the docs that I dealt with at Mayo the one I wanted to pay attention and dig for info was the nephrologist and he was the one that wouldn't do anything. I was really disappointed - but I feel there is a kidney connection and wish someone would look into it. I practically begged him on behalf of all POTS patients to do more research and look into this for us and it fell on deaf ears. I tried!!!!

Issie

[Clairefmartin]

Issie, what about contacting the nephrologist in this article:

'Every step is a battle’ The disease: Postural Orthostatic Tachycardia Syndrome, or POTS

I'm going to my first Endo apt with a POTS Specialist name Dr Vinik next week, so this was a great thread to read, thanks for all your hard work.

Claire

[issie]

Claire,

Thank you for the article. I will look into it a little more. It looks like he's mostly treating children and is treating the normal flow type of POTS. I'm pretty sure I'm low flow and know I'm HyperPOTS with high bp's and high noriepi. I'm in the catagory of the opposite type of treatment than the majority of POTS people. I don't know if he is treating any of us in that subset. That's my biggest problem - so many less of us in that catagory.

Issie

[issie]

On another thread we were talking about salt loading and florinef use. The article I read in regard to the rats is listed in this article I wrote a long time ago. It list the source.

Issie

[hholmes13]

Thanks for bumping this. issie that's a really interesting article! Crazily enough, I work on the same floor as a lady who routinely tests catecholamines and renin/aldosterone/angiotensin and vasopressin levels. She wanted to check all my levels for me to try and get some answers. Unfortunately my veins were not cooperating and we only got enough blood for the catecholamines. I'm still waiting for those results. I told her I'd like to her to try again to get my blood because I would like to know those other levels as well. It sees like it would be a good thing to know. Interesting ideas about salt loading not necessarily being the best thing. I think I may push my co-worker to check that stuff for me sooner rather than later....

[issie]

Levels won't be correct if you're salt loading and/or on florinef - will not give a true reading.

Issie

[Annaliese]

Issie. I reread this and want to say a couple of things. First, i agree with you re major salt intake being a waste of time. I tried a high salt diet for a few months and two things happened- a) my OI didnt improve at all and my vertigo got worse. I stopped taking the salt because i had done some research on aldosterone and hearing issues and like you found that low aldosterone levels could contribute to hearing problems. I couldnt see anything on vertigo and low aldosterone though. I also have the same worries about florinef- taking too much and my kidneys not bothering to make aldosterone anymore. I am currently trying to get off florinef altogether. Recently i had my renin, aldosterone and ang II levels tested in hospital. I am getting them redone when off florinef. I dont know what to make of the results really. Renin, aldosterone and ang2 are all low when lying and all high when sitting. So in my case there doesnt seem to be any problem in making these substances. Also, i had a short synacthen test and that was normal. One thing id like to say about blood volume is that endurance elite athletes can have blood volumes 30% greater than the norm. 30%! That's amazing. I wonder whether people able to recumbentl exercise would be better off doing just that than chugging down the salt. Who knows. We are such a mixed group its so hard to work out what's going on. I for one am getting sick of reading medical material- i think ive understood something then i realise, nope, ive got no clue. For me, at the moment im sticking to recumbent exercise, naltrexone and the min amount of florinef i can tolerate without fainting. At least with exercise theres no negative associated with it (unless you do to much of course). I made the mistake of doing too much exercise once and it made me ten times worse - i assume this was an AI response to stress. Btw, have you seen anything on vertigo and aldosterone levels?

[Annaliese]

Ha ha. How did that face get in the middle of that text!

[issie]

It's cute - don't worry about it. LOL

I haven't read anything about aldosterone and vertigo - but vertigo can be affected by the ears too and if aldosterone can affect hearing - looks like it could affect that to - maybe connected to the ears causing the vertigo - but, it may have to do with fluid levels in the head. Just downloaded the two books by Dr. Diane Driscol and reading those - finished the first one and on the second one. Interesting ideas about POTS/EDS/ and MCAS and too much fluid in and around the brain and problems with lymph drainage. It's on sale on amazon right now - on kindle - I don't have a kindle - but you can download it to your computer. Interesting read so far.

I wonder why lying your levels were low and upright high? Did you find any answer on that? Mine were very low/nearly non-existant sitting.

Issie

[Annaliese]

Yep, already got it on kindle but havent read it yet. Was just looking at what happens if you block ang II receptors. Looks like your body just makes more Ang II. Ha ha. Fits in with your theory about why not to take huge amounts of salt- your body will just make adaptation to it. http://www.nature.com/ajh/journal/v13/n2s/abs/ajh2000665a.html

Ive been thinking about the low lying levels of all three hormones. Either ive got an endocrine AI disease or a AI neurological disorder. Just say i have a neurological disorder increasing sympathetic drive. That would increase vascular resistance and therefore my endocrine system would be behaving appropritely in decreasing blood volume because ive effectively got less vasculature to fill. So then when i stand, the blood rushes to my feet as it does in anormal person but my vasculature is already at max construction levels so this mechanism effectively doesnt work anymore. Hr goes up to compensate, blood volume increasing hormones are excreted because local low blood volume is detected. Or, ive got an endocrine AI disorder. One would think though that if i had this then id end up with strange ratios of renin/ aldosterone renin/ ang II, aldosterone ang II like in that stewart paper. Cant quite think of a sensible endocrine scenario...... You got any ideas?

[issie]

There are different opinions on what is going on with us. I keep thinking there is an endocrine disorder myself - but, I've been told that the way my body is responding could just be a compensatory thing. (Not from a doctor - but, a very smart and intelligent person - who I value their opinions.) It could be that - but, if the high blood pressures and high NE levels are there to up my blood volume and increase directional flows of blood - I wish what was causing the issue in the first place would straighten out. With those high surges in NE and the anxiety that brings with the tacky with the slightest amount of bp drop - it's hard for a person to take when it happens nearly hourly. If mine is related to EDS veins and laxity of my veins - then there isn't much I can do about that - that will not be something I can fix. (If that was it, it seems that vasoconstricting veins would be the best thing for that - but, that would bring your bp levels up. And, I haven't done well on any of the things I tried that vasoconstricted. If it was laxity of veins - seems like that would have helped and/or worked - -- when in fact, those were some of the worst things I've tried in my journey.) So, if I can't fix it - what do I do about it? See - Annaliese - we're all in a dilemma - we have such complex issues caused by so many different possibilities and some of the things we can't fix. It's just trying to figure out what is the best way to deal with an imperfect body to give us the best quality of life.

I was just talking on e-mail with another friend of mine who has issues with low aldosterone levels and she was telling me that those with Addisons when their aldosterone is replaced - if their renin levels are normal - they actually feel a whole lot better --- that being replaced. With us with POTS - that doesn't seem to help a whole lot - some get a little better - but are no where near well. So, there must be more to it than that. Could renin be the issue? Doubtful - because most POTS people have normal renin levels but low aldosterone levels. Then there's me with both of them low - why? Not sure. But, doc's are saying they can't do anything about it becaues of my having POTS. What is normally done is betas and diuretics (according to the Mayo doc, If both are low.)

As for blocking Ang II - some are doing that and it's helping. The difference is - the ones that it's working for don't seem to have issues with their renin/aldosterone levels (if I'm remembering right) Usually, at least the renin level would be good because of the chain of events to get your Angiotension II levels high in the first place - if it goes through the kidney pathways. Angiotension II can also be produced in the liver and heart - so, having high levels may be coming from a different place - not kidney - but, haven't seen a whole lot written on that or saying that. Just know it can be produced elsewhere. But, if you're low in NO (nitric oxide) and need to increase potassium levels an ARB could be beneficial and has been to some. (Lots of talk on lorsartan - in recent and past.) That's a whole other subject that could be bumped up. You see, you start looking into one area and that leads you to something else and then to something else. Let's face it - our body is all connected and when one thing goes wonky - a lot of stuff can go wonky.

I hope we or the docs can figure it out. Not having sucess with any doctors in regards to this system and the connection to POTS. No one wants to touch it. I still think it's very relevant and there must be something being missed. I don't know what it is - but, thinking something is there yet to be discovered.

Issie

[ramakentesh]

1. All the patients with elevated Ang II have low renin and aldosterone.

2. As ive explained the elevated angiotensin II in 20% of POTS patients appears to be a genetic defect - because the enzyme that converts it through catabolism is not present.

3. Normal renin levels? 20-25% have low renin levels and most have normal (but abnormal considering low blood volume or regional hypovolumia).

[issie]

If you look at the pathways that leads to Angiotension II levels from the kidney - in order to have high or adequate levels of angiotension II the first part of the pathway is renin. (This was explained to me by the nephrologist at Mayo - he said that even some doctors don't understand this.) There is renin - then - angiotensinogen - then angiotension 1 - then angiotension 2 and finally aldosterone. http://en.wikipedia....otension_system

Angiotension can be made in other organs too and that makes you wonder if the high levels are coming from some place other than the kidney pathway. If these levels (renin and aldosterone) are low in POTS patients and there is high angiotension II - why is that the case - how does this happen? It doesn't appear to be through the kidney pathway.

I've also brought up the idea that some of the dysfunction could be at the liver level. Some of us have issues with our livers and the liver does release angiotensiogen. There is another thread with this question having been posed in the past. But, we never really dis-sected the idea very far.

In a normal person and if the kidney pathways are followed - logically if there is low renin there should be low angiotension II levels. But, in SOME POTS patients there is low renin and low aldosterone (there is some sort of paradox) - I'm not sure that the ones who are on this site - have had their angiotension II levels measured. It has been assumed that there is an issue and they are trying lorsartan and it is helping. (There may be one guy - that knows for sure - Lenna - your son - were his levels too high and what was his renin and aldosterone levels?) Many of us have attempted to have our angiotension II levels measured but have been met with resistance from our doctors (for some reason) and we don't know what our levels are. (With me the lorsartan was not a good fit for me - maybe because I already have low renin and aldosterone - maybe my angiotension II levels are low too. I don't know what those levels are. But, the lorsartan gave me horrible chest pains - like heart attack feelings that went into my arm and jaw.) But, there are a few who are doing beautifully on this med. It will up NO (nitric oxide) levels - this is good for some POTS people - not so good for others. It is thought that low flow people are low in NO levels and would benefit in an increase - but OI or the more common form of POTS is already too high in NO levels and this may not be good for them. http://www.nymc.edu/...Flow%20POTS.htm

Issie

[Lenna]

In a normal person and if the kidney pathways are followed - logically if there is low renin there should be low angiotension II levels. But, in SOME POTS patients there is low renin and low aldosterone (there is some sort of paradox) - I'm not sure that the ones who are on this site - have had their angiotension II levels measured. It has been assumed that there is an issue and they are trying lorsartan and it is helping. (There may be one guy - that knows for sure - Lenna - your son - were his levels too high and what was his renin and aldosterone levels?) Many of us have attempted to have our angiotension II levels measured but have been met with resistance from our doctors (for some reason) and we don't know what our levels are.

Issie, you're right - we met with resistance when we tried to get Dan's Ang II level measured and we don't know what it is. We do know that his renin and aldosterone were normal. Yet Losartan has been working really well for him.

[issie]

Thanks Lenna for the feedback - that was what I had thought I remembered. I don't believe that Jangle knows what his levels are either - if I remember right about him. I know, Jangle is liking Lorsartan too. So, at least in one persons case there was normal renin and aldosterone, unknown angiotension II levels and the ARB is of benefit.

Issie

[ramakentesh]

1. Lenna - Losartan may work in any setting where there is sympathetic excess and by implication low nitric oxide levels. AMDA and other competitors are being investigated in this regard and elevated angiotensin II only account for a percentage of patients potentially. However even this is debated, because other research groups have found intact postural responses to postural hypotension in POTs patients with nitric oxide blockade.

That being said there are three papers by the doctors who first identified elevated angiotensin II in POTS that demonstrate that all these patients (with documented high ang II) there was paradoxically low aldosterone and renin. You can read them for yourself. This perhaps accounts for the low blood volume in these patients.

Edited May 4, 2012 by corina

[ramakentesh]

It will up NO (nitric oxide) levels - this is good for some POTS people - not so good for others. It is thought that low flow people are low in NO levels and would benefit in an increase - but OI or the more common form of POTS is already too high in NO levels and this may not be good for them

Among many effects, but be careful of assuming NO level abnormalities are a proven etiological mechanism in POTS. There is disagreement about this point. Also upping NO isnt as simple as you suggest. NO has many effects. there may be normal expression of some forms of NO but low bioavailability at one level only. The research on elevated NO in POTS is two studies whereas others have reported no change in orthostatic responses in POTS patients with NO blockade, suggesting it does not play a role.

[issie]

1. Lenna - Losartan may work in any setting where there is sympathetic excess and by implication low nitric oxide levels. AMDA and other competitors are being investigated in this regard and elevated angiotensin II only account for a percentage of patients potentially. However even this is debated, because other research groups have found intact postural responses to postural hypotension in POTs patients with nitric oxide blockade.

That being said there are three papers by the doctors who first identified elevated angiotensin II in POTS that demonstrate that all these patients (with documented high ang II) there was paradoxically low aldosterone and renin. You can read them for yourself. This perhaps accounts for the low blood volume in these patients.

I ran across some ponderings from an e-mail that I got from a person who researches POTS and seems to be most of the time spot on about his theories. He was thinking that the angiotension II could be high because of a falty gene that doesn't take it out of the body correctly and with the two studies done on high angiotension II - both of those papers showed that the people had low renin and low aldosterone levels. His ideas are that lorsartan would work on most anyone that is low NO levels and is vasoconstricted - regardless of what their angiotension II levels are. I found this very interesting - it is just a theory with no proven studies (as far as I know) but, just wanted to throw this idea out there for something to consider. Since there seems to be a paradox in this with low renin and low aldosterone with high angiotension II levels - in this study - this would explain the paradox - in theory - because angiotension II can be produced elsewhere in the body besides the kidney pathway. (Thanks RKT for your insights)

Issie

[bellgirl]

Wow, Issie...I'm impressed...I think I'm going to have to read this many times before I get it all (if I get it all...lol) By the way, I am on Losartan because of my vasoconstriction because of my high blood pressure, before I was diagnosed with dysautonomia...

[issie]

Thanks Kimbrellgirl, This is an old thread - but, I put a lot of research into it. It was something I first started questioning when I first got diagnosised. I still dont' really have the answers about it. I think there is some sort of connection and it hasn't been figured out yet.

Issie