No Levels Impacted By Histamines?

[Clairefmartin]

A lady I know whose kids have MCAD and POTS compiled some really interesting research, would love opinions on this (sorry if its already been discussed, I searched the forum and didnt find much):

"OK, I wonder if I may be on to something here. At the very least, I’m learning a lot. Please post your thoughts.

We know that Nitric Oxide levels tend to be high in POTS patients, as seen here:

Cutaneous constitutive nitric oxide synthase activation in postural tachycardia syndrome with splanchnic hyperemia.

http://www.ncbi.nlm....pubmed/21642500

(Splanchnic hyperemia is blood pooling in the stomach)

Flow-mediated vasodilation and endothelium function in children with postural orthostatic tachycardia syndrome.

http://www.ncbi.nlm....pubmed/20643249

Nitric Oxide also is shown to be increased in patients with migraines:

Increased asymmetric dimethylarginine and nitric oxide levels in patients with migraine.

http://www.ncbi.nlm....pubmed/21359872

Nitric oxide supersensitivity: A possible molecular mechanism of migraine pain.

http://psycnet.apa.o.../1994-14066-001

And in patients with CFS/ME:

Kindling and Oxidative Stress as Contributors to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

http://www.ncbi.nlm....les/PMC3022475/

(This is an excellent and thorough article that points to oxidative stress as a factor in autonomic function.)

As well as Multiple Chemical Sensitivity:

Elevated nitric oxide/peroxynitrite mechanism for the common etiology of multiple chemical sensitivity, chronic fatigue syndrome, and posttraumatic stress disorder.

http://www.ncbi.nlm....pubmed/12000033

In fact, Nitric Oxide’s role is multifaceted, and an excessive amount can lead to neuronal injury:

Nitric oxide in health and disease of the nervous system.

http://www.ncbi.nlm..../pubmed/9246670

Neurobiology of nitric oxide.

http://www.ncbi.nlm..../pubmed/8978984

Including Mitochondrial dysfunction:

Nitric oxide-induced mitochondrial dysfunction: implications for neurodegeneration.

http://www.ncbi.nlm....pubmed/12543245

Nitric oxide, mitochondria and neurological disease

http://www.sciencedi...005272898001686

So what causes high levels of Nitric Oxide? Histamine? Quite possibly:

Nitric oxide: a regulatory mediator of mast cell reactivity

http://journals.lww....st_cell.47.aspx

Nitric oxide accounts for histamine-induced increases in macromolecular extravasation

http://ajpheart.phys...6/6/H2369.short

Nitric Oxide and Histamine Induce Neuronal Excitability by Blocking Background Currents in Neuron MCC of Aplysia

http://jn.physiology.../2/656.abstract

Nitric oxide production in human endothelial cells stimulated by histamine

requires Ca2+ influx

http://www.ncbi.nlm....pdf/9480877.pdf"

[ramakentesh]

it all looks very tidy but there are a couple of points missing.

MCAD has been - at least in the literature - connected with hyperadrenergic POTS or low flow characteristics. Recent work by Stewart/Medow suggests that low flow patients tend to have reduced expression/bioavailability of at least neuronal nitric oxide levels. Thus low flow states may be characterised by impaired or reduced NO levels.

Elevated angiotensin II levels have been found in plasma of a large subset of patients tending towards low flow/hypovolumic states. has your friend considered the possibility that angiotensin II (which has many varied effects throughout the body) plays a role in mast cell activation/abnormalities?

Hyper patients also tend to haev abnormalities in beta 2 adrenoreceptor function which also has a roll in mast cell processes.

Elevated neuronal NO levels - which is possible in the normal flow group - might tend to lean towards a reduction in sympathetic outflow rather than the opposite. Again, the MCAD paper talks about hyper presentations. histamine or other active peptide release might instigate NO mediated vasodilation in this area or there could just be increased NO activation alone.

NO being one of the main vasodilating molecules is used by many vasoactive substances to vasodilate. Histamine vasodilation is mediated by NO, calcitonin gene related peptide, substance P and other potential vasodilators also all seem to use nitric oxide.

But there is another vasodilating molecule that could also have a role in some POTS - hydrogen sulfide.

Assymetric Dimethylarginine is a competitor of arginine and thus increases in its levels would be expected to result in reduced NO bioavailability rather than the opposite.

The fact that NO is involved in migraine doesnt tell us very much because any of the inflammatory vasoactive chemicals involved will probably instigate release of NO to vasodilate as a consequence rather than cause. One study found that migraine patients could experience a migraine with the administration of calcitonin gene related peptide. it would be expected that NO is elevated where there is cerebral vasodilation. But why this occurs is probably more relevant to the etiology of migraine - abberant serotonin activity and vasoconstriction, release of inflammatory mediators, hypersensisation to NO mediated vasodilation, pain.

[Clairefmartin]

Did you just whip that response out off the top of your head??? Why are you not working in a lab somewhere (or are you?)? I have a bio lab background and feel a little spaced out and am drooling a bit from reading all this

In other words - thanks Rama! We need to start sending your thoughts to these researchers! So basically any number of checmicals could be triggering the NO and causing vasodilation, or a lack of NO causes vasoconstriction?

[RichGotsPots]

I'm not well versed on NO as I should be, but looking around for a non-drowsy muscle relaxant I saw something that was interesting.

http://en.wikipedia.org/wiki/Neuromuscular-blocking_drug This page lists adverse affects of this type of medicine and it says "hypotension

(transiently), by release of histamine

^{[11]" I don't think NO is involved or at least they don't mention it but they do mention "i}nhibition of acetylcholine"

never heard of BP being regulated by release of histamines. That would seem like a link between MCAD and Dyautonomia, but like I said I don't know much about it..

[ramakentesh]

Some researchers dont think NO has any effect or relation to POTS but others think it does in at least some cases.

I guess my points where that the MCAD thing appears connected to hyper/low flow presentations rather than ones where there is likely too much NO. Histamine and other substances involved in MCAD might cause vasodilation through release of NO.

The theory is that too much NO causes vasodilation and reduced sympathetic activity; too little causes the opposite. There may be vasoconstriction and flow abnormnalities.

[issie]

Yeah Rama, your mind never ceases to amaze me and your knowledge is far beyond what any of us can comprehend. Glad you're here to give us insight.

Issie

[Clairefmartin]

thanks!

[ramakentesh]

I just read lots...

[brethor9]

Rama, I agree with the hyper pots...beta adrenergic part.....this is what I tested positive for and now I am being investigated for Mast Cell issues....I strongly feel they are all related that way.... I just wonder like everyone else what sets it all in motion to begin with?

[issie]

Breathor9, That's the million dollar question. Don't we wish we knew. I do think that MCAD and EDS and POTS are proving to have close connections for many of us - me included.

I just read lots...

Keep on reading, my friend, and don't forget to share with us.

Issie

[corina]

genetics maybe?

although i've had problems all my life, not knowing what caused them, i learned that after every surgery i had under ga i got worse. of course i didn't understand what was happening and it was always brushed off. after i had surgery in 2001 dysautonomia hit real hard and got worse over the years which lead to a diagnose. so for me surgery under ga is certainly a trigger and maybe a cause??? it's so difficult to figure this all out and there's so much to learn. thanks everyone for sharing so much info!

[brethor9]

Corina

That is a valid thought about the GA.....I also have gotten worse after every GA surgery I have had....I have had 4 in the last 9 years......my neurologist once told me that anasthetic is incredibly hard on the nervous system and that it can affect it long after you think it has worn off. My very first symptoms started not to long after giving birth.....just another piece in an unsolved puzzle.....

Bren

[Chaos]

My POTS specialist says surgery can be a trigger for neuropathies as well. Since I have autonomic neuropathy and my POTS etc started after surgery, that's what he's attributing it to. However, he thinks that I had a genetic pre-disposition to it (which is where the EDS comes in, in his opinion.)

I just read lots...

Yeah, but you remember it, which is what I find so difficult to do! LOL

[ramakentesh]

Some people tell me that their POTS is caused by autonomic neuropathies whereas others tell me that their neuropathy is improving now they are on medications to treat POTS - in other words that their neuropathy is a symptom of POTS rather than the other way around.

Im curious how people decide this. Based on their own hunch? Repeating what their doctor told them?

[sue1234]

Reading about y'all feeling worse after multiple surgeries makes me think that I have read years ago that general anesthesia can lower your vitamin B-12 levels. Low B-12 can cause neuropathies. Have y'all had yours checked lately?

[RichGotsPots]

Some people have told me that they have had good results with taking antihistamines like zantec and claritin. I think I've had a very slight improvement. But I've taken singulair for months without any noticeable improvement. So that's why I think my histimines are dysfunctional and maybe not my mast cells. That's just my own experience, but I want to get tested for MCAD eventually.

My allergy tests showed normal IgE levels, but my IgG levels were low. I wonder how IgG levels have to do with histimines, maybe nothing because my allergist didn't mention any connection...

Anyone know of any histimine dysfunctional things besides MCAD, where mast cells aren't involved?

[DoozlyGirl]

Some people tell me that their POTS is caused by autonomic neuropathies whereas others tell me that their neuropathy is improving now they are on medications to treat POTS - in other words that their neuropathy is a symptom of POTS rather than the other way around.

Im curious how people decide this. Based on their own hunch? Repeating what their doctor told them?

Rama and others,

My autonomic neurologist diagnosed orthostatic hypotension and autonomic neuropathy (CV and sudomotor) based off my autonomic testing (TTT, TST, QSART, Valsalva), yet my HR doesn't rise more than 20 beats when changing postions. I haven't been diagnosed with POTS, yet others on this site wonder why not. I do not meet the 30 bpm criteria. My HR is not my issue, but my BP is. My BP is normal or low when laying (110/70 - 120/80) and climbs while sitting (130/90 - 210/110max) then plummets while standing (60/40 - 80/60). Even with my BP dropping from 166/100 to 88/60 in a minute or two, my HR doesn't usually rise more than 20 bps. My symptoms only got worse on zabeta and verapamil but can abort the labile BP, flushing and GI evacuation with antihistamines.

I am finding that mast cell activation is likely causing my autonomic neuropathy. I don't believe POTS is part of my equation. What am I missing here?

Thanks, Lyn

[DoozlyGirl]

Anyone know of any histimine dysfunctional things besides MCAD, where mast cells aren't involved?

Check out histamine intolerance.

[Maiysa]

And for me ditto what Doozlygirl said. But I haven't tried the MCAD treatment yet. Still working on diagnosis, even though tryptase came out to 11 again. I also don't have POTS. I used to when I was battling a serious lung infection and toxic thyroid for a few years. But I do have hypo orthostatic intolerance. I never know the difference between that and POTS. Sorry I get confused lately, easier than usual. But Rich that is a good question, what other tests are there for Mast Cell. My IgG or however this is written came out normal, but not the tryptase. But IgE or something like that came out abnormal, saying I'm sensitive to infections. But nothing serious...knock on wood.

[RichGotsPots]

@Rama- where did you read about the hyperPots and Mast Cell connection? I get tested next week for adrenaline which I firmly believe is a big cause of my problems, yet I'm worried because my BP can drop when I walk and it tend to be high during surges... so dont know what meds will help the most.. I firmly believe that I dont have MCAD though and I've seen tests from 1 person at the Mayo who has HyperPots and thinks they have MCAD because antihistimines help but the test said no. That's why I think maybe there is a link with Histamines and not directly with Mast Cells...

[issie]

@Rama- where did you read about the hyperPots and Mast Cell connection? I get tested next week for adrenaline which I firmly believe is a big cause of my problems, yet I'm worried because my BP can drop when I walk and it tend to be high during surges... so dont know what meds will help the most.. I firmly believe that I dont have MCAD though and I've seen tests from 1 person at the Mayo who has HyperPots and thinks they have MCAD because antihistimines help but the test said no. That's why I think maybe there is a link with Histamines and not directly with Mast Cells...

It is really, really hard to get a firm scientific test/proof of MCAS being the issue. Many times, it just can't be caught with science. There is a new way of testing tissue from an endoscope with a certain stain that Dr. Afrin is doing and he says it's over 90% accurate for picking up mast cells. Usually, there has to be a bone biopsy. Many of us with HyperPOTS seem to have issues with MCAS being part of the issue. Not sure - it's all the issue - but the H1 and H2's seem to help as does Nasal Crom and things to help with histamine isssues. (Vit C, Quercetin and others)

As for your bp dropping when you walk - so does mine. I think because it is increasing the flow of pooled blood in the legs and that helps the blood pressure issues. When I stop and stand still things go back up. I also have low bp when I lie down. I have high NE levels and high bp's mostly. So, it's a hard spot to be and even harder to treat. You need them to test your dopamine, NE and epi levels - both lying and standing. Then you will know what those ranges are.

The docs tell us to see if the treating with H1 and H2's help and if it does ---great. We may have a probable before the DX and not a confirmed DX - but, in all likelyhood - it is positive. Wish, the testing that Dr. Afrin is doing was more easily available to us.

There is also a possilbe problem with histamine intolerance - and I did a thread on it. There are things that can block DAO and that can create issues with histamine intolerance. So, we don't want to do things that block DAO.

Issie

[RichGotsPots]

Issie- what were your supins levels versus your orthostatic levels? If Rama is right then Mast cells or histamine levels might be affecting NE or E levels or vise versa, hmmmm...

I wish we could know for sure if it is pooling. Have you ever tried a combo of midodrine and a antiadrenic BetaBlocker at the same time? Because what else stops pooling besides midodrine? Well octreotide does in the stomach but I polled an not many people took it on the forum to get conclusive results..