Why Does Taking Nitroglycerin Tablets Help Me?

[janiedelite]

So I recently posted about being in the hospital with bad pressure on my chest, chest pain radiating into my left arm and jaw, and high BP. In the hospital, my troponin level went up to .35 (I think normal is less than .1) and troponin is an indicator of heart muscle damage. I'm 36, no family history of heart disease, low cholesterol, but I've had chest pain off and on for the 3 years I've had POTS. One benefit of staying in the hospital this time was I met a cardiologist who wants to work with my Mayo doc and try to treat me. I've had ECG's and chest xrays before to rule out a heart condition, but everything's been normal til this elevated troponin. They sent me home from the hospital with a bottle of sublingual nitroglycerin and I took it twice today for chest pain. It nearly eliminated my pain for a good hour after taking it, and the pain was mild for several hours following. I did have a mild headache for a few minutes, but I felt better overall than I have in years. I had 4 doses of nitro in the hospital and had the same effect.

The cardio is completely baffled as to why I benefit from nitro when my ECG's are normal.

I have chest pain at rest and it worsens when I talk, but doesn't get much worse with activity usually.

SO, the nitro lowers my BP a bit, as expected. Why do I feel better (more alert, more energy, breathe more freely) after I take it? Am I having inappropriate vasoconstriction in my chest for some reason which the nitro must help?

I have abnormal pooling (you can see it when I lower my arms or legs), so I'd think that I should feel horrible on this medication. I'm not expecting medical advice, just your thoughts on this!

[ramakentesh]

Ive been secretely waiting for someone to report their results from having taken any of the nitric oxide donors and their POTS.

There are four mechanisms in which low nitric oxide have been implicated in POTS.

Firstly a subset of patients tested by Dr Marvin Medows and Dr Julian Stewart were found to have hypovolumia, high angiotensin II and as a consequence low neuronal nitric oxide. High angiotensin II potentiates the vasoconstrictive effects of norepinephrine and effects the vasomotor nerves some how causing pooling. it has been suggested that the onset is gradual in this variety usually and that its caused by a genetic defect where angiotensin II is not converted into its metabolite properly or something along those lines.

This is LOW FLOW Pots and its definately worth checking out in your case.

The second mechanism is pretty similar except that the cause of the reduced nitric oxide is from chronic inflammation as found in CFS - inflammation increases plasma levels of c-reactive protein, which reduces the 'catabolism' of angiotensin II and the same result as above.

Finally it could be possible that a hyperadrenergic state where norepinephrine is constantly constricting arteries and veins could deplete nitric oxide levels at the endothelial level?

There could also be a problem with the nitrergic nerves in the heads of some POTS patients causing problems with cerebral vasoregulation.

Confusing but that is fantastic new potentially in your case.

[ramakentesh]

There has been an ongoing argument about whether the reduced blood flow to the heart and resultant reduced stroke volume in POTS is because of excessive vasoconstriction or veno pooling. Your results in this context may be quite telling. Certainly worth contacting a few doctors about if I were you.

[erik]

I've got a few quick thoughts... questions really... I always end up with more questions than answers:

There is a chance of you having better pulse pressure. Meaning systolic dropping a little and diastolic dropping more. Heart looking less active, but in fact being more efficient (plus we're ignoring pulse). Ignoring the chest pain, did your subjective sense of feeling better happen to correlate with widening or narrowing here?

One simple angle on this is that nitroglycerine is said to dilate veins more than arteries. Arteries pump out, veins return/drain. Physical pressure in vascular bed is not the only factor to permeability (it seems a great number of things influence that), but it might be one factor... permeability might feed pooling a bit. Regardless, the "load" on the heart is reduced by this... the presumption behind the relief it brings. BP should go down... and it doesn't necessarily mean less blood is getting out to the body.

POTS seems characterized by "uneven perfusion" (not sure if that's validated but seems to be the case). If something is magically evening perfusion, a better overall outcome could result even with less total perfusion (again, less perfusion being a potentially false assumption of lower BP). How local needs are "assessed" seems pretty complicated...

If the artery vs. vein ratio is actually important... I'd be curious to know more about it. Are nerves segregated (I'd guess not, but don't know); Is there a variance in the multitude of receptors that get multiplexed into a "constriction state"; Are the non-neuronal messengers distinguishing them and tuning neuronal response; Is an implicit distinction of a vein drawn simply from a natural change in it's contents, and this concentration used to modulate constriction response; etc. I assume I'm asking a very simple anatomy question... just enjoying pondering it before learning what's really going on!

[mkoven]

I think this is probably confirmation that you are having vasospasms/prinzmetal, but that the spasms aren't severe enough to change your ekg? I feel worse on nitro, but ((knock on wood)) feel better on my norvasc- midodrine-florinef combo. I think in my case I spasm to counteract excessive dilation--maybe your ratio of constriction /dilation is somewhat different.

It's great that the nitro works for you. There are a couple other people here with spasms. I can't remember who it was, but someone else who takes florinef for pots and cardizem for spasm. It's a tricky balance. When I tried to increase the norvasc from 2.5 to 5.0, I felt terrible--exhausted and lightheaded. It took a little while for me to get used to the 2.5, but it really is fine for me.

[janiedelite]

There is a chance of you having better pulse pressure. Meaning systolic dropping a little and diastolic dropping more. Heart looking less active, but in fact being more efficient (plus we're ignoring pulse). Ignoring the chest pain, did your subjective sense of feeling better happen to correlate with widening or narrowing here?

POTS seems characterized by "uneven perfusion" (not sure if that's validated but seems to be the case). If something is magically evening perfusion, a better overall outcome could result even with less total perfusion (again, less perfusion being a potentially false assumption of lower BP). How local needs are "assessed" seems pretty complicated...

If the artery vs. vein ratio is actually important... I'd be curious to know more about it. Are nerves segregated (I'd guess not, but don't know); Is there a variance in the multitude of receptors that get multiplexed into a "constriction state"; Are the non-neuronal messengers distinguishing them and tuning neuronal response; Is an implicit distinction of a vein drawn simply from a natural change in it's contents, and this concentration used to modulate constriction response; etc. I assume I'm asking a very simple anatomy question... just enjoying pondering it before learning what's really going on!

VERY interesting. One of my first POTS symptoms was chronic frostbite. I easily get purple toe tips and chilblains (fingers too) which never happened prior to POTS. I also have visible venous pooling, though; my legs/arms don't swell but they sure turn mottled and purple. Mayo said it was impossible to differentiate in cases like mine where inappropriate constriction and pooling ends and begins (in which blood vessels).

My pulse pressure does increase slightly. It's usually 15 to 35 standing and with nitro it's 40 to 55. Thanks for your informative response.

[janiedelite]

I think this is probably confirmation that you are having vasospasms/prinzmetal, but that the spasms aren't severe enough to change your ekg? I feel worse on nitro, but ((knock on wood)) feel better on my norvasc- midodrine-florinef combo. I think in my case I spasm to counteract excessive dilation--maybe your ratio of constriction /dilation is somewhat different.

It's great that the nitro works for you. There are a couple other people here with spasms. I can't remember who it was, but someone else who takes florinef for pots and cardizem for spasm. It's a tricky balance. When I tried to increase the norvasc from 2.5 to 5.0, I felt terrible--exhausted and lightheaded. It took a little while for me to get used to the 2.5, but it really is fine for me.

Yeah, I was prescribed cardizem for my frostbite issues once but my EP cardio (who diagnosed my POTS) said it would make me feel worse by too much vasodilation. Also, I think it's a prinzmetal variant probably exacerbated or caused by low-flow POTS/nitric oxide deficiency... but that's just a guess after reading all of your responses.

I'm taking a nitro 0.4mg sublingually evey 4-5 hours for the past two days. That's TOTALLY NOT how it's meant to be given. But it's not like I have crushing chest pain occasionally when I'd take one or two for that episode. Most days, I have mild to moderate chest pain. I've always thought it was not a good sign that it often radiated down my left arm, but after telling so many docs about it and ECG's are all normal... well, you know

[janiedelite]

Rama, we're so blessed to have you here posting on DINET! I was hoping you'd put in your two cents. Mayo said I had post-viral POTS (from when I had mono 6/06), but my first tachy episode wasn't til 10/06. I was fine til then. Since then, I've had a gradual decline in function and increase in symptoms. I asked Mayo about this, but the neuro said it wasn't a coincidence that I had mono 4 months before my first attack.

We know that I produced excess norepi on standing. Now in the first mechanism for low-flow POTS you mentioned, would those people be born like this and always have POTS symptoms? Because I was fairly normal until the age of 32. I do believe I have CFS, and the nitro makes me feel more awake if you can believe that! Now, I get some symptom relief when lying down, especially from the fatigue and dizziness. But the chest pain is NOT relieved when lying down. And my norepi levels are normal when supine.

Should those of us who have low-flow POTS petition our docs for some nitro and record our results here? just kidding!!!

[firewatcher]

Rama, we're so blessed to have you here posting on DINET! I was hoping you'd put in your two cents. Mayo said I had post-viral POTS (from when I had mono 6/06), but my first tachy episode wasn't til 10/06. I was fine til then. Since then, I've had a gradual decline in function and increase in symptoms. I asked Mayo about this, but the neuro said it wasn't a coincidence that I had mono 4 months before my first attack.

We know that I produced excess norepi on standing. Now in the first mechanism for low-flow POTS you mentioned, would those people be born like this and always have POTS symptoms? Because I was fairly normal until the age of 32. I do believe I have CFS, and the nitro makes me feel more awake if you can believe that! Now, I get some symptom relief when lying down, especially from the fatigue and dizziness. But the chest pain is NOT relieved when lying down. And my norepi levels are normal when supine.

Should those of us who have low-flow POTS petition our docs for some nitro and record our results here? just kidding!!!

No, actually you need Viagra...I'm not kidding!

[janiedelite]

No, actually you need Viagra...I'm not kidding!

Makes sense, really! So I wonder which one will raise more eyebrows at the doctor's office when I ask for it?

[erik]

Nitro is mentioned as one of the provocative drugs sometimes given during TTT. Anybody here happen to have had that done?

Safety Sam says nitrates are "absolutely contraindicated" for use with PDE5 inhibitors (Viagra, et. al.)... so be sure not to combine! I'm sure you wouldn't anyway, but Safety Sam likes to say stuff like that! Seems like PDE5 selective inhibitors might miss the problem constriction zone for thankful (though perhaps in a fun way . Seems PDE6 is retina or something, PDE11 perhaps testes/prostate? Is there a PDE<x> out there matched to the region where thankful tends to overconstrict? Something else with that "selectivity" profile?

This article... after lots of biochem details... surmises:

To be useful for the symptomatic treatment of angina pectoris, however, the drug would need to be targeted more to venous than arterial smooth muscle. Despite the desire to avoid tolerance, it may be a difficult task, indeed, to come up with an overall better antianginal drug than the 130-year-old nitroglycerin.

Do other anti-anginal drugs manage this balance at this point... in their peripheral dilation effects?

[erikainorlando]

My EKG's are always abnormal after activity and normal after periods of rest. So..on one of my trips to the ER, they gave me nitro following my abnormal EKG. It helped me too. I felt better immediately with the chest pain and pressure. Are your EKG's abnormal on being upright or with activity?

I don't take it obviously on a normal basis. I always have chest pain after being upright...but if I lay down my chest pain will go away...

Anyway...I am not really so inclined to make heads or tails of much of the constriction information...(I get am embarrassed to admit I just get confused)...but this is my personal experience.

Erika

[janiedelite]

Thanks, Safety Sam!

Don't worry, Erika. My brain feels as thick as mud sometimes when I'm trying to follow some of the research these guys put together. I read it again, and again, and again... But my EKG's even during the stress test were normal. I've never had an abnormal EKG. And I always have chest pain on being upright, too, some days more than others. But I often have chest pain at rest also. It just seems to linger. It's even there when I first wake up in the morning. I took a nitro today after waking and it went right away. Amazing.

[ramakentesh]

Low Flow POTS is associated with a gradual onset but the genes that are implicated could possibily cause it from birth.

Basically it appears that the ACE 2 gene is not functioning so that angiotensin II is never 'catabolised' and it effects nitric oxide at the neuronal level by decreasing its bioavailability. Something similar happens in heart failure. The result is that the vasomotor nerves are effected causing pooling, but also reduced neuronal nitric oxide results in potentiation of norepinephrine - super excessive vasoconstriction. Pooling and vasoconstriction, cold skin and hands, reduced overall blood volume and relative hypovolumia because of constriction and increased venous permiability.

There is a fair bit of info in this on the web if you do a search on low flow POTS.

Whether LOW FLOW POTS could also be caused by inflammation is still theoretical although the research is all there - c-reactive protein definately causes increased angiotensin II levels. Elevated angiotensin II levels causes increased oxidisive stress and reduced nitric oxide at the neuronal level. result is sympathetic excess.

There is the other alternative - constant vasoconstriction from impaired norepinephrine clearance results in nitric oxide being bled dry. This is possible in NET deficiency. The vascular system is primarily constricted by alpha 1 receptors and to a lesser extent possibly beta 1 receptors - norepinephrine being the constrictor. Angiotensin II increases norepinephrine release and potentiates its effects. Dilation is ultimately governed by endothelial nitric oxide release. All the vasoactive peptides that cause vasodilation do so by releasing nitric oxide. beta 2 receptors are also involved in vasodilation but purely in the stomach and vital organs during fight or flight (which would potentially result in a presentation quite like POTS).

In the head vasodilation is governed PURELY by the nitrergic nerves. Excessive cerebral vasospasms could occur if these nerves were depleted of nitric oxide either endothelial level or at the neuronal level.

I mention the beta 2 receptor because in the theory where POTS is caused by excessive beta receptor excitement, you have peripheral and cerebral vasoconstriction with stomach and thoratic vasodilation in theory - but I think the role of beta 1 receptors is still contentious in vascular systems and there are other things that I dont quite understand in this area.

Sorry if this is a little rambling. I had a coffee before LOL... And it goes WAY to my head...

At the end of the day - it makes sense but from the excessive vasoconstriction stand point.

VERY interesting. One of my first POTS symptoms was chronic frostbite. I easily get purple toe tips and chilblains (fingers too) which never happened prior to POTS. I also have visible venous pooling, though; my legs/arms don't swell but they sure turn mottled and purple. Mayo said it was impossible to differentiate in cases like mine where inappropriate constriction and pooling ends and begins (in which blood vessels).

yeah I get that as well when its acting up. Stewart et al demonstrated that the bluing is the result of reduced cutaneous blood flow - reduced blood flow to the skin. its still impossible to determine why this occurs - why does the blood flow reduce to the skin?

High flow POTS results in hot, swollen extremities - true pooling looks like this. However, if the body uses adrenaline to counter act this it causes a vasospasm similar to raynauds - its all too confusing and ultimately what MAYO said about it is 100% right.

[janiedelite]

Yesterday I had the best day I can remember since my POTS started over 3 years ago. We got up at 3am and shopped for 6 hours, then hubby napped while I wrapped gifts. Then lunch with my brother, cut down the Christmas tree and decorated it, the house, and strung lights in the yard. Then out to dinner with family and played board games til 10pm. All of this I did while taking the nitro every 4-5 hours. I could immediately tell when it started to wear off. I get sluggish and tired and the burning/tight/sharp chest pains return. My husband had to nap during the day, and he was astonished at how well I was functioning with no nap! Yes, I was tired because of lack of sleep. But normal tiredness is NOTHING like the fatigue and pain I've constantly endured over the last 3+ years. It seems like nitro is a miracle drug for me.

Question: Can I become tolerant of the nitro? Will it not be so effective for me in a while if I continue to take it through the day?

Thanks for the ramblings, Rama. I so miss my coffee! Haven't touched caffeine in 3 years because it worsens my symptoms. Interesting what you said about the cerebral perfusion because I never had migraines before POTS. And yes, I was initially diagnosed with Raynauds after my skin biopsy came back as pernio/frostbite. But I never presented with the classic sudden-onset of vasoconstriction. Rather, my hands and feet are either too warm or too cold (and either bright red, or pale and slightly dusky) all the time. It makes sense if the purplish mottling of my legs is a sign of decrease bloodflow to my skin, that my chronic frostbite issues of my feet is just an exacerbation of that vasoconstriction.

I'm hoping that my new cardiologist will hear back from my Mayo neurologist, who might realize the significance of my improvement on nitro and prompt further investigation into my inappropriate constriction/dilation. As it is, Mayo just recommended that I treat my pooling issues (with compression, salt, fluids). All those measures HAVE been helpful, but they never got me to the level of functioning that the nitro has accomplished.

[janiedelite]

Okay, I've noticed the past 2 days that after I take my mestinon timespan in the morning that I have worse chest pain and tightness, I had had to take the nitro more frequently in order to make the chest pain tolerable. So I googled "mestinon and chest pain" and there were results stating mestinon can cause chest pain/tightness and blue extremities. Maybe the mestinon is worsening my tendency for inappropriate vasoconstriction???????? I'm not going to take it tomorrow and we'll see what happens.

[ramakentesh]

i always cringe with medications - our responses are so overly inappropriate to vaso-active medications. Its a fascinating result. If you speak to the people at Mayo maybe you should mention to them Dr Stewarts/Marvin Medow's works on nitric oxide as well as Vandy's current study on the role of the nitric oxide system and Chronic OI.

Not saying they wont be aware, but it might give them some background.

I dont think you will become tolerant to NO - it is possible, but unlikely. There could be side effects from increases NO - particular postural hypotension which we would all assume through conventional explanation of POTS should not be helpful LOL.

Dr Robertson et al stated in a 2006 study that Vandy dont believe that any of the current explanations of POTS explain all of the manifestations apparent.

[ramakentesh]

Some links that may be of interest:

http://www.circ.ahajournals.org/cgi/conten...HA.104.526764v1

http://ajpheart.physiology.org/cgi/content...act/293/4/H2161

http://journal.shouxi.net/html/qikan/nkx/g...418_200327.html

In the third, Vandy found that certain nitric oxide genetic makeups resulted in worse POTS. There conclusion was that perhaps Nitric oxide is decreased neuronally but increased endothelial level:

The orthostatic tachycardia and hyperadrenergic state in POTS are also consistent with less NO activity in the central nervous system. eNOS and neuronal NOS are expressed in the central nervous system, where NO acts in the rostral ventrolateral medulla and the nucleus tractus solitarii to decrease BP, HR, and urinary NE excretion.5253,54 These brain regions are involved in the baroreflex response to orthostatic stress,55,56 and impaired baroreflex function has been proposed to underlie the increased central sympathetic outflow and the postural tachycardia of POTS.57

And some more speculative links:

http://books.google.com.au/books?id=z_QRCc...;q=&f=false

http://www.prohealth.com/library/showarticle.cfm?libid=9765

http://www.chronicfatiguetreatments.com/wo...e-nitric-oxide/

[mkoven]

since you tolerate nitroglycerin, one possibility might be for your docs to rx you a nitro patch--it would give you a slow steady dose, and might prevent attacks. I think you're not supposed to wear it 24/7, or you could become tolerant. It didn't work for me, and just gave me a headache and made me tachy. but then ntg doesn't work for me either.

[janiedelite]

These brain regions are involved in the baroreflex response to orthostatic stress,55,56 and impaired baroreflex function has been proposed to underlie the increased central sympathetic outflow and the postural tachycardia of POTS.

Thanks, Rama! I did spend a couple hours yesterday afternoon reading all of Dr. Stewart's research on NO. I think the above quote from Vandy is interesting because it implicates a CNS defect, rather than just peripheral neuropathy. The genetic research regarding NO was interesting too. I really don't understand all of the biochemistry, but I'm muddling through it!

I read all of the pharmacy inserts whenever I get a new medication, and I remember that mestinon can cause smooth muscle cramps. I normally have PMS-related cramps, but since I've been on mestinon they've been about 3-times worse than normal. Also, mestinon is contraindicated in folks with asthma. However, there has been research lately that mestinon can preserve heart muscle in folks with narrowed coronary arteries... I'm going to call my pharmacist this morning when they open and ask about my recent increase in chest pain.

Yes, I do experience a drop in BP (pretty mild with just one pill)/headache/worse OI and tachy symptoms with nitro. But the benefit far outweighs the side effects for me. They gave me a combo of nitro paste and pills in the hospital. I really do notice that the nitro pills help for about the same duration as the paste, with the same intensity and duration of side effects. I'm going to call the cardiologist to let him know how regularly I've been taking the nitro (I really hope it doesn't scare him off!).

Thanks so much to all of you who are muddling through this with me!

[tinkerbella]

I used to take nitro for the chest pains. Then when I couldn't take the BB and needed meds for my raynauds they said that the cartia xt and the cardim er were like taking nitro in a slow release form. It gave my hands, feet, and nose some great relief from the cold weather or cold pools, help with the

tightness in my chest/pain and yet I was at the top of the dosage and still needing something for maxium cirulation relief.

The meds helped with my BP but did contribute to some thachyness. The Nitro gave me headaches and the cartia xt did not. Eventually the neuro suggested I be off all generics as she felt many people do best on the brand name drug.

The drugs ( mestinon/ clonidine ) with the cartia xt, fight each other my doc tells me. With one opening the blood vessles and the other is tightening them. Now we've added 1/4 of a bb due to being allergic to see what will happen.

Today, I'm so tired....

http://www.labtestsonline.org/understandin...ponin/test.html

found this to add for understanding you blood test levels....

wishing you the best of luck.

bellamia~

[janiedelite]

The drugs ( mestinon/ clonidine ) with the cartia xt, fight each other my doc tells me. With one opening the blood vessles and the other is tightening them. Now we've added 1/4 of a bb due to being allergic to see what will happen.

Bella Mia,

thank you for replying when you're so tired! I hope you start perking up soon. Yes, that's exactly what I was wondering was happening when I took the mestinon and it seemed the nitro wasn't working as well. I hope that after finding out how well my body does with a vasodilator that my cardio is willing to try some meds out on me.

I hope you do well with the BB.

Take care, Janie

[tinkerbella]

Thankful,

Your very welcome, i'm working here laying down on my side with my bed table and laptop right beside as always...

bellamia~

[ramakentesh]

The drugs ( mestinon/ clonidine ) with the cartia xt, fight each other my doc tells me. With one opening the blood vessles and the other is tightening them. Now we've added 1/4 of a bb due to being allergic to see what will happen.

Potentially but not necesarilly - Clonidine actually has a vasoconstrictive action in some cases, but more often it results in a general decrease in sympathetic tone. Its still unclear why mestonin helps - the first theory was that by improving musco and nico receptor stimulation it was giving a double boost to the parasympathetic system and also decreasing sympathetic tone, but the second theory was that it was vasoconstrictive in cases of distal/patchy neuropathy.

So they might be working against each other but they might not be if you get me.

[janiedelite]

Ugh... this chest pain is really getting to me. I tried not taking nitro last night, but just took a bit of vicodin and around 10pm I began to feel wierd, cold and tingly and spacey alternating with the deep aching chest and jaw pain, like I did last Tuesday prior to going to the ER. My BP was 120/60 at 9pm but by 10:30 was 141/95 standing and lying. So I took a nitro and got immediate relief. But since last Tuesday's similar episode resulted in elevated troponins, I was afraid to go to sleep in case I wouldn't wake up in time to get to the hospital if something really bad was happening. I really need a better solution than the nitro tablets which only help for an hour or 2. I just know the standard protocol when you call the doctor with symptoms like mine and they send you to the ER. But I really need some relief.