Latest Research Out Of Vandy

[sue1234]

I was in Pub Med and found this latest research paper from the usual researchers out of Vandy. I read it, but don't quite understand it. I really know nothing about angiotensin I or II. I do, however, know that I have had a low aldosterone. Can anyone understand this enough to make a guess if this is something fixable? Can someone's "angiotensin II" be measured? Is it low because of our orthostatic physiology OR is it low for no reason, and fixing it could help the POTS? I hope it is fixable!

http://www.ncbi.nlm.nih.gov/pubmed/21266211

By the way, my cardiologist needs this article slipped onto his desk. I think he hasn't seen this one yet...or, hasn't taken the time to read it!

http://www.ncbi.nlm.nih.gov/pubmed/21087570

[TXPOTS]

Dr. Stewart and his team were the first to find elevated ang II levels in some POTS patients. I believe these were patients from his "low flow" category. I had my ang II level measured and sent to the same Quest lab that Dr. Stewart used. Mine was low, not high. I also had low renin and low aldosterone, so I was curious if I could fit this category. I have not read the full text of this new Vandy study, but it would be interesting to know how they measured ang II. I was on a high sodium diet at the time, and I noticed sodium levels were controlled. Theoretically, an angiotensin receptor blocker, like losartan, may be helpful. I have been prescribed losartan, but I am too fearful to try it since my ang II levels were not high.

[sue1234]

I went to Labcorp's site to read about angiotensin II, and it talked about how it had to be immediately in a refrigerated centrifuge, and the "shelf-life" of the sample was 1 day, unless frozen! So, makes you wonder if the tests that are this delicate are always handled properly.

It would be interesting to know what your levels would have been if you had not been on a high-salt intake.

I'm just thinking how tied together it is with aldosterone. Here, all I've known about aldosterone was its connection with low cortisol in Addison's disease. I hadn't looked at it from its own perspective--involved intimately with the kidney only. I was thinking it truly would only be low if one had Addison's.

[TXPOTS]

I went to Labcorp's site to read about angiotensin II, and it talked about how it had to be immediately in a refrigerated centrifuge, and the "shelf-life" of the sample was 1 day, unless frozen! So, makes you wonder if the tests that are this delicate are always handled properly.

It would be interesting to know what your levels would have been if you had not been on a high-salt intake.

I'm just thinking how tied together it is with aldosterone. Here, all I've known about aldosterone was its connection with low cortisol in Addison's disease. I hadn't looked at it from its own perspective--involved intimately with the kidney only. I was thinking it truly would only be low if one had Addison's.

Exactly, I am skeptical the sample was handled with such diligence.

[nunntrio]

I was in Pub Med and found this latest research paper from the usual researchers out of Vandy. I read it, but don't quite understand it. I really know nothing about angiotensin I or II. I do, however, know that I have had a low aldosterone. Can anyone understand this enough to make a guess if this is something fixable? Can someone's "angiotensin II" be measured? Is it low because of our orthostatic physiology OR is it low for no reason, and fixing it could help the POTS? I hope it is fixable!

http://www.ncbi.nlm.nih.gov/pubmed/21266211

By the way, my cardiologist needs this article slipped onto his desk. I think he hasn't seen this one yet...or, hasn't taken the time to read it!

http://www.ncbi.nlm.nih.gov/pubmed/21087570

Thanks for posting this study. I think this must be the angiotensin study I took part in last year. They would not give me my test results but, I will contact them now and request them since the study had been published. Do you know how we get the full text version of the report? I can say that I was on a very controlled salt diet for the test and it was one of the most miserable tests I have ever had done. It involved having an IV in each arm and having to pee in a bed pan while laying down. YUCK!!! I know they actually paid me $200 to do one test while I was there and I think this is the one.

[TXPOTS]

Thank you for taking part in the POTS study, nunntrio. I would love to see the full text as well. Dh may have to make a medical library trip. Goodness, I would want to know what MY results showed, or at the very least, get a follow up call before the study came out.

[sue1234]

Nunntrio, really, peeing laying down? But, it was all for a good cause!

Yes, it would be interesting to see what your levels were at. Do let us know if you find out.

Based on your visit, were they able to give you a treatment guideline, and did it help you?

[nunntrio]

TXPOTS - If your DH find a copy of this study please let me know. I just emailed Vandy to request my results. I wish they had been proactive enough to have let me know this information as well.

Sue - Yes peeing lying down(not easy). I guess these hormone levels can be detected in urine and can are effected by posture. I will let you know if I find anything form Vandy. I emailed them and they are pretty good about replying. As to wether Vanderbilt helped I can say they tried(I knew going in there was no majic pill). They recommended first a beta blocker then a beta blocker in combo. with Midrodine(they said Florinef would not help because I have normal blood volumn). Unfortunately I was not able to tolerate either. I did not leave there really feeling any better phyically but I did benefit in some ways. First, I got a definite diagnosis of POTS which having a firm diagnosis was a huge relief. Secondly having it from Vanderbilt made it hold a lot of weight with my local Doctors. They were also able to rule out certian causes (low blood volumn for one, now possibly angiotension)which was helpful.They also recommended to my local to have a Qsart to rule our small fiber neuropathy (which also came back normal). If you would like any further infor. I can PM you.

[Lenna]

Sue,

Here is my understanding of the role of Angiotensin II in POTS. This explanation may be a bit simplified, but like the rest of you, I'm trying to learn about things that are outside of my field of expertise (whatever that is...).

There are many steps in the Renin/Angiotensin/Aldosterone process which regulate blood pressure and fluid volume in the body. One of these steps involves the conversion of Angiotensin II  to ACE 2. If you have too much Angiotensin II because the conversion to ACE 2 isn't happening, then your blood vessels will be too constricted.

Most people with POTS have the opposite problem - their blood vessels are too dilated. That's why the first medications they're given when they are diagnosed with POTS are vasoconstrictors like Midodrine.

Another thing that helps most POTS patients is drinking lots of water and taking in lots of salt. However, if the RAA chain of events is disrupted by the inability of Angiotensin II to convert to ACE 2, then you will have low blood volume regardless of how much you drink and how much salt you eat.

Dr. Stewart in NY has given a name to the subset of POTS patients whose blood vessels are too constricted and whose blood volume is always low. He calls this "Low Flow POTS". Low Aldosterone and low Renin are also typically found in people with Low Flow Pots.

If things like Midodrine, Mestinon, fluid & salt loading, compression socks, etc., are helping you, then I don't think that Angiotensin II is something that you need to worry about. On the other hand, if all the standard POTS treatments don't help or are actually making you feel worse, then you might want to talk to your doctor about Low Flow POTS and Angiotensin II. You can Google "Julian Stewart" and "Low Flow POTS" to find lots of articles about his studies. 

Dr. Stewart has been testing a medication called Losartan for Low Flow POTS. It is an Angiotensin II antagonist. My son recently started taking it. It's a bit premature for me to report that it's a success for him, but I can say that he has been seeing some benefits so far and that we're still playing with the dose. If it seems to be really helping him a few months down the road, I'll post a detailed report about it on this forum.

I hope this helps. 

Lenna

[sue1234]

Lenna, thanks for that info!

It makes me sad to read that, in a way :

"If things like Midodrine, Mestinon, fluid & salt loading, compression socks, etc., are helping you, then I don't think that Angiotensin II is something that you need to worry about. On the other hand, if all the standard POTS treatments don't help or are actually making you feel worse, then you might want to talk to your doctor about Low Flow POTS and Angiotensin II."

I haven't had a doctor offer me anything except a beta or alpha blocker, which both made me feel worse. No one has looked in depth into the aldosterone issue I had. No one has offered to try me on other meds. They just say "there's not much that can be done for POTS".

In other words, I haven't had "all the standard POTS treatments" tried on me yet, and I'm a million doctors and 5 years into this!

It gets so discouraging when doctors don't want to read up on this condition and learn what the latest tests and/or treatments are.

[juliegee]

Thanks for the simplification, Lenna. I needed that! After reading Dr. Stewart's work, I think I am low flow. Tell me about the losartan. How does it work?

Thanks-

Julie

[sue1234]

Okay, I am trying to understand this. Low Flow POTS is vasoconstriction due to decreased blood volume related to low renin and low aldosterone?

So, reading up on Losartan, I see this:

"Losartan is a selective, competitive Angiotensin II receptor type 1 (AT1) receptor antagonist, reducing the end organ responses to angiotensin II. Losartan administration results in a decrease in total peripheral resistance (afterload) and cardiac venous return (preload) All of the physiological effects of angiotensin II, including stimulation of release of aldosterone, are antagonized in the presence of losartan.'

So, if we initially have low aldosterone, then how would this help? Wouldn't relaxing the vessels with a still-reduced volume just cause way too low blood pressure? I guess I can't "see" how it would help. But, as I stated earlier, this is all new to me, and I am trying to understand this.

[Lovebug]

This is some interesting stuff! I also find it ironic (although I don't know for sure if I'm hypovolemic) that I'm extremely sensitive to volume depletion and I often have orthostatic symptoms when I'm dehydrated. But the ironic part is that my BP goes UP (not down) when I get this way. I've posted a little bit of info below on the Renin-angiotensin system so that some may understand it better. I'd also like to know how cortisol plays in to all this b/c I had an unexplained high level of cortisol (the stress hormone) but was negative for Cushings.

"Renin is an enzyme secreted into the blood from specialized cells that encircle the arterioles at the entrance to the glomeruli of the kidneys (the renal capillary networks that are the filtration units of the kidney). The renin-secreting cells....are sensitive to changes in blood flow and blood pressure. The primary stimulus for increased renin secretion is decreased blood flow to the kidneys, which may be caused by loss of sodium and water (as a result of diarrhea, persistent vomiting, or excessive perspiration) or by narrowing of a renal artery. Renin catalyzes the conversion of a plasma protein called angiotensinogen into...angiotensin I. An enzyme in the serum called angiotensin-converting enzyme (ACE) then converts angiotensin I into....angiotensin II. Angiotensin II acts via receptors in the adrenal glands to stimulate the secretion of aldosterone, which stimulates salt and water reabsorption by the kidneys, and the constriction of small arteries (arterioles), which causes an increase in blood pressure. Angiotensin II further constricts blood vessels through its inhibitory actions on the reuptake into nerve terminals of the hormone norepinephrine."

Encyclopedia Britannica retrieved 2/7/11 from http://www.britannica.com/EBchecked/topic/498140/renin-angiotensin-system#

[Crow]

I did a "pee while laying down" study at Vandy - I wonder if it is the same one? Messy LOL.

Vandy's studies are done in a research hospital, with it's own lab. I don't know how the samples are handled but the pee etc ends up there.

Vandy also is studying losartan for Marfans syndrome aneurysms - I don't think it has been studied for Ehlers Danlos aneurysms but some folks take it anyway.

http://www.mc.vanderbilt.edu/reporter/index.html?ID=6557

[nunntrio]

Vandy just emailed my results. My Ang II was 32.1 and Ang (1-7) was 10.6. My Ang II level was very close to the control values. Bummer...yet another thing that is NOT causing my POTS.

[sue1234]

Bummer...yet another thing that is NOT causing my POTS.

This is the first time using the "quote" in reply, so don't know if it worked.

Funny, funny!! We sooo know what is NOT causing our POTS!! Still looking for that elusive cause....

[sue1234]

""I also find it ironic (although I don't know for sure if I'm hypovolemic) that I'm extremely sensitive to volume depletion and I often have orthostatic symptoms when I'm dehydrated. But the ironic part is that my BP goes UP (not down) when I get this way.""

From what my brain thinks, when we are low volume, no big deal if we are sitting or lying down. But, stand up, and (I forget exactly) about 15% of our volume goes into our lower body. Our brain is not getting enough blood flow and then the body goes into a panic mode and vasoconstricts. This causes the b/p to go up, up, up. In my mind, I think once it vasocontricts, I have too much blood that had "settled" in my limbs and now has a hard time getting back up due to the vasoconstriction. But, that's just my thought. I kind of witness things like hot and swollen feet and hands at those times.

""I'd also like to know how cortisol plays in to all this b/c I had an unexplained high level of cortisol (the stress hormone) but was negative for Cushings.""

I have had a high cortisol once before, but normal the others. I think cortisol is just trying to help us out as our body is in such a turmoil all the time.

""Renin is an enzyme secreted into the blood from specialized cells that encircle the arterioles at the entrance to the glomeruli of the kidneys (the renal capillary networks that are the filtration units of the kidney). The renin-secreting cells....are sensitive to changes in blood flow and blood pressure. The primary stimulus for increased renin secretion is decreased blood flow to the kidneys, which may be caused by loss of sodium and water (as a result of diarrhea, persistent vomiting, or excessive perspiration) or by narrowing of a renal artery.""

Could there be something that causes our renin-secreting cells to sense that we have high b/p, and thus the lowered/normal renin and lower aldosterone? Do we have narrowing of thr renal artery? Has anyone ever had their kidneys extensively worked up? I have not.

SORRY, I HAVE NOT LEARNED HOW TO USE MULTI-QUOTES. I RESPOND IN BETWEEN THE ABOVE QUOTES.

[Lenna]

Honestly, reading and deciphering the medical studies is like trying to decipher Chinese for me...I wish I could explain how the Ang II and Losartan affect hypovolemia but I really don't get it myself. The RAA system seems to be the most complicated thing I've come across. I'll be thrilled if Dan's hypovolemia improves, but I'll be ****** if I understand why it happened.

I need things laid out for me in very simple terms. I know that Ang II is a potent vasoconstrictor and if ACE2 doesn't convert it to Ang 1-7, then you are never going to get to the point of producing Nitric Oxide, and your blood vessels will be too constricted. This is what I believe is happening to my son. Dan participated in a clinical trial last summer at Beth Israel Hospital which confirmed that he probably is not producing sufficient Nitric Oxide. He has never had his Angiotensin II level tested.

Dr. Stewart is still conducting studies with Losartan, so I guess it would be fair to say that this is an experimental medication for Low Flow POTS. Somehow, by blocking Ang.II receptors, the Losartan is supposed to correct the faulty RAA system.

Danny hasn't been taking this long enough for me to say definitively that he is better. He does seem to have a little more energy, a little less dizziness, and most dramatically he has a lot less brain fog. This is the only medication he's taken in the past 3 years that hasn't made him feel worse. He's still on a pretty low dose of Losartan and is increasing it very slowly. We don't really know what the optimal dose will be. After every increase, it seems to take a couple of weeks or more before he feels the effects. So this is a slow process for him that requires patience.

And Yes, now low blood pressure is an issue. His blood pressure is now all over the place. It can be good - 120/80, and then bad - 90/70; but the interesting thing is that he can feel bad when his blood pressure is good, and he can feel good when his blood pressure is bad. It doesn't seem to correlate. His doctor told him to stay on salt pills, even though they are contraindicated with Losartan because there is a risk of too much Potassium. But without the salt, his blood pressure might really get too low. So now Dan has to have his electrolytes tested frequently.

I'll keep you up-to-date on this, because I'm hoping that it can be a really important breakthrough for some people with POTS.

[sue1234]

Hey, whatever works!! That is good that SOMETHING helps him. Definitely keep us posted.

[Lovebug]

Hey Sue,

I sorta agree. I think the cortisol ties in to the fact that the autonomic nervous system controls all these hormones so it's just another thing to be abnormal. Also, the BP increase could be due to an increased catecholamine release in response to the orthostatic changes that you mention...

As far as the high BP affecting the renin angiotension system, I think it has more to do with blood flow to the kidneys (poor perfusion) but what is causing the poor perfusion? And where does all our volume go? I drink more than 4L/day and don't urinate excessive for that amount. I wish I could just understand that concept, LOL!

I've never had a renal ultrasound or other testing but any time we get our electrolytes checked, kidney health is assessed through the BUN/Cr and mine has always been normal. I do have pain in my flank area but that could be virtually anything related to dys.

[TXPOTS]

Bummer...yet another thing that is NOT causing my POTS.

This is the first time using the "quote" in reply, so don't know if it worked.

Funny, funny!! We sooo know what is NOT causing our POTS!! Still looking for that elusive cause....

LOL Nunntrio and sue, That's how I felt when I got my ang II levels, and countless other tests.... After my last appointment, I told them out of frustration that I was done until the researchers go back to the drawing board and come up with some new ideas. I think I'm just as likely to find what works for me. No more medication experimentation for now.

[roxie]

I had mine done at the request of Dr Stewart. Was told there was no abnormality but after reading these posts about how you need to freeze it & stuff I wonder if mine was handled properly? The girls at the lab didnt even know what angiotensin or plasma renin were they had to look it up online.

Does anyone know where else it can be done properly beside Vandy?

[nunntrio]

Funny, funny!! We sooo know what is NOT causing our POTS!! Still looking for that elusive cause....

LOL Nunntrio and sue, That's how I felt when I got my ang II levels, and countless other tests.... After my last appointment, I told them out of frustration that I was done until the researchers go back to the drawing board and come up with some new ideas. I think I'm just as likely to find what works for me. No more medication experimentation for now.

I think I am getting to that point myself. I am starting to feel like a human guinea pig and it is draining. We will see.

[issie]

Hey all. I haven't been here in awhile. Go back and look up the research done awhile back on the renin, aldesterone, salt topics. All connected. I personally think that the connection between noriephrine and aldesterone is a key component. If you are hyper POTS you probably have high noriephrine levels and low aldesterone - it's a counter balance. If you upped your aldesterone levels it possibly would up your noriephrine levels higher and then there would be more panic type symptoms and higher BP's. Maybe our body is lowering things for a reason. But, on the other hand - if you have more orthostatic issues with lower BP's than possibly upping your aldesterone levels would be beneficial. I wrote a lengthy paper on this and it wasn't published in the newsletter because I question how doctors are treating POTS patients. I also don't think that salt loading is the correct thing to do - it lowers aldesterone levels even more.

[sue1234]

Hey Issie, you have been gone a while! Good to see you back. I'm not sure how I understand the aldosterone/norepinephrine connection. I do know that people with a pheo(high norepinephrine) have low blood volume. I was assuming their aldosterone would be low, thus keeping their volume low. I think it is all confusing, for sure! The ONE thing I know with absolute certainty is I don't know enough!

I know my aldosterone isn't low from salt, because I am one who doesn't use extra salt. So I'm wondering why the lower aldosterone to begin with? What in our body is miscommunicating and why?