POTLUCK

I got my lab results for these 3 back. They were done while on Inderal 140 a day, but prior to adding Losartan to it. Angiotensin II 13 ( Low. In normal range ) ( lab < or = 86 norm.) Aldosterone 4 ( In normal range ) ( lab < or = 28 norm ) Plasma Renin Activity ( 0.84 In normal range) ( lab 0.25-5.82 ng/ml/h norm.) Angiotensin II is not elevated as it often is in low flow POTS (89 avg in Dr. Stewarts study), in fact it is lower than the average normal in Dr. Stewarts study (32.) Renin (PRA) was not low as it often is in low flow POTS, in fact it is awfully close to the (.90) average for normals that Stewart found. On graph of correlation between renin and aldosterone they correlate on line. http://www.nymc.edu/fhp/centers/syncope/angiotensin_in_pots.htm These data do not suggest low flow POTS. It could be... 1. I do not know if being on B-blocker can affect. 2. I was not impressed that the lab had any experience doing this. 3. Stewart did find some low flow POTS patients with low angiotensin Overall though, these labs do not support my theory of having low flow POTS, which does not make me happy, as I would like to see the picture come together not fall apart. My free fractionated catecholamines Lying and standing are pending, but the B-blocker can definately affect those results- though to what degree I have no idea. I would have preferred to have them done off B-blocker when I had my tilt. The Losartan has not made me any worse and possibly is helping. I am currently taking 25 BID with upward titration over time planned. I am pretty sure it has lowered the BP lying and standing a little. Although I hope the data is useful to someone, this post is also to vent that the Angiotensin did not come back high and support the low flow theory. Thanks for listening/ ( reading )

25 BID now might be improvement, might not, hard to say as the days vary alot. I am not worse, and no major side effects. Thank you for asking.

http://www.nymc.edu/fhp/centers/syncope/he%20Metabolism%20of%20Ang-II%20by%20angiotensin%20converting%20enzyme-II%20(ACE-II)%20is%20defective%20in%20Low%20Flow%20POTS%20causing%20a%20reduction%20of%20the%20vasodilator%20Ang-(1-7).htm See picture- it is complex but I like the picture explanation. Angiotensin II appears to have an affect via both receptor types and its breakdown product. Or there may be a problem in some cases with the breakdown via ACE2 ( by antibodies? ) or by a polymorphism for the Angiotensin 2 type 1 receptor itself such as this correlation in MVP http://www.ahjonline.com/article/S0002-8703(00)70015-9/abstract or the connection with Ang 2 type 1 in Marfans http://www.nejm.org/doi/full/10.1056/NEJMc081528 The above article on Diabetic retinopathy seemed to suggest that as iNOS was upregulated baseline NO went down. So it is not clear to me that what happens locally will have the same effect on the whole system. "To say there is reduced nos is also to say there is a regional angiotensin ii elevated concentration" may depend if it affecting the type 1 or 2 receptor if I am not confused ( which I may be ) http://www.ncbi.nlm.nih.gov/pubmed/18182246 http://www.ncbi.nlm.nih.gov/pubmed/10691781 http://www.ncbi.nlm.nih.gov/pubmed/9218502 However with all that confusion added my idea is IF I have the low flow POTS the losartan may increase NO levels and decrease peripheral resistance. I do not know if I have the low flow type. When are you starting it. I heard your running was helping. I always feel good while running which I suspect is NO and the faster HR, but the last time I ran my HR was elevated for hours afterwards. I have never had syncope so upright exercise is a possibility for me.

Rama, I thought that Dr. Stewart showed that there were 3 categories of flow in POTS patients and that the average low flow POTS patient has considerably higher Angiotensin 2. (89±20 vs 32±4 ng/L), http://www.nymc.edu/fhp/centers/syncope/angiotensin_in_pots.htm but also that blocking Angiotensin 2 type 1 receptors caused vasodilation through a mechanism that was inhibited by a nitric oxide inhibitor, suggesting that at least on a local level the vasodilation of Ang 2 type 1 receptor blockade has to do with nitric oxide. http://ajpheart.physiology.org/content/294/1/H466.short My understanding is the Ang 2 type 2 receptor may increase NO as seen in the picture here http://www.nymc.edu/fhp/centers/syncope/he%20Metabolism%20of%20Ang-II%20by%20angiotensin%20converting%20enzyme-II%20(ACE-II)%20is%20defective%20in%20Low%20Flow%20POTS%20causing%20a%20reduction%20of%20the%20vasodilator%20Ang-(1-7).htm I have found several articles suggesting Angiotensin 2 affects NO by researchers other than stewart but the entire system is clearly a very complex one in which NO affects all sorts of things including NE itself. I am trying to understand some of it.

Thank you

Diabetic Retinopathy and increased nitric oxide ( very interesting.) I do not know how you remember these things. I could not find my article (argh) so I googled the subject. I found this article suggesting increased NO as you said http://www.molvis.org/molvis/v15/a242/ but I found this suggesting this may not be the case. ( This article gets a bit complicated for me. ) http://diabetes.diabetesjournals.org/content/47/6/945.short It seems to be suggesting that as iNOS was upregulated baseline NO went down. This kind of interaction ( i.e. complicated ) between iNOS, eNOS, and nNOS may have a great deal to do with the different affects in POTS and in related areas such as CFS and mast cell disorders. nNOS is a neurotransmitter, particularly important in the hypothalmus, yet Dr. Stewart's research states specifically it was the nNOS and not the eNOS that was affected in low flow POTS. Reference... http://www.nymc.edu/fhp/centers/syncope/nNOS%20in%20low%20flow%20POTS.htm

Rama, Yes, nerve damage due to the Diabetes could be the entire problem in my case and that is of course a good thought. However, I developed the dizziness in Dec 2009 right when I was diagnosed with the Diabetes ( and my sugars were not bad -mostly under 150 ) As the dizziness got worse so did the diabetes. ( cause effect or neither ? ) but when the sugars went high ( 300's for peaks ) I got them down in a couple months, so not much time for nerve damage. ( Also eyes, kidney, peripheral nerve testing for touch etc. are all good. ) I use Actos, though doubt it does much just continue it for now not to rock the boat but endo also feels a trial without it later is a good idea. What keeps the sugars down is low carb diet. Jenny Ruhl's approach. http://www.phlaunt.com/diabetes/index.php As I have learned more about NO I have found reference to diabetes decreasing NO but insulin increasing it. The low carb diet does not stimulate the insulin ( part of the idea for the diabetes ) but this may mean less insulin to increase NO. Low NO could even be worsening the DM http://www.nfb.org/Images/nfb/Publications/vod/vod212/vodspr0613.htm http://diabetes.diabetesjournals.org/content/55/1/102.abstract In this article they use BH4 to increase NO and decrease DM 2 effects. http://www.springerlink.com/content/6lyab59mpa6qg3nm/ This is another interesting article suggesting a stabilizing effect directly on the SA node of NO http://george-eby-research.com/html/taurine-l-arginine-arrhythmias.pdf I thought I had one on NO decrease and the eye in DM but maybe not, as I can't find it. Since we were talking about NO and the sun a day or two ago, I will throw this one in I just came across. Hope no one minds too many links. http://eurheartj.oxfordjournals.org/content/early/2010/03/09/eurheartj.ehq069.full

I woke up at 5AM and could not sleep so took a second 0.5 Klonopin ( 1mg total which I prefer to avoid but did not get to sleep till midnight ) , put on my sports watch for a HR monitor and went back to sleep ( An hour later ) Anyways my HR ( on Inderal Long Acting 80AM and 60PM ) was averaging ~85 sleeping but did go into the 100's for several periods. ( You can see it on the computer screen later. ) I looked at Dr. Grubb's article above ( thank you Rissy2D ) but I do not understand how you know if you have IST. Off meds my HR must go into the 100's sleeping even more often ( as 140mg is a lot of Propranolol ) and I know lying awake off meds it goes in and out of the 100's off medication, but it goes up on tilt ( or standing ) On my test it went above 140 but oscillated repeatedly ( going to 156 and down to 80 ) per the nurse. Your sister has the IST diagnosis? Does her HR rise from lying to standing?

You can get a BP cuff for $20-30 at most drug stores that work well. This will tell you if your pressures run high like mine or you are losing pressure when you stand like many people do also, and gives you a chance to do your tilt test at home different times of the day, after trying something new etc. Obviosly you want to consider safety with the standing part.

With me it is not the BP as this remains high lying and standing even on the whopping dose of 140mg total per day.

My B-blocker Propranolol is very similar to Nadolol. ( B1, B2 no alpha block ) I find it reduces what I call the "mountain lion in the room feel" as HR goes lower ( off RX as high as 156 but bouncing a lot ) When my HR gets below about 100 standing ( which runs about 75 Lying at that point ), if I lower the HR more I feel very lightheaded and more brainfog, hard to think. The problem is it does not evenly affect me, all day, even though it is the long acting it starts stronger in about 3 hours and then wears off by end of day. Thus I feel more brainfog type symptoms early in the day and more fatigue with this, and more "mountain lion in the room, but less brain fog later in the day. I take the long acting 80 in the morning and 60 at the night. I recently tried 60 in the morning, and felt better all morning but HR hit 115 standing by 2PM and I had to add 10 mg regular acting twice in afternoon.

Too bad, that sounds like it would be worth testing and can't be that hard.

I agree with seeing the doc. you could try the "Poor mans tilt test". Lying HR and standing HR, do the blood pressures for 5-10 minutes each. I hit the button after each one and it comes out about once a minute. See if the HR is greater than 27 point difference. 9 They use 30 on tilt which is equivalent to 27. This way you can see wht the BP is doing also, and why you might have syncope. Might do it when someone else is there on the carpet.

ramakentesh, ganglionic acetylcholine receptor antibody was detected in 14.6% ( Can these be tested locally-labcorp, Quest etc.? )

Ramakentesh, You seem to have an amazing amount of knowledge on these things. The problem with stewarts work that is published is that he is only showing a local response due to microdialysis injections, and not what happens when you affect the whole system. I still appreciate that he is doing the research. He seems to be currently giving Losartin to patients that test as low flow to see what happens but that study goes till 2014. I figure I will just try it now. ( 25 BID today - no clear benefit or worsening yet.) I am also taking vitamin C 500 BID. You mentioned " all forms of low flow states - increased orthostatic BP and increased MSNA" I am thinking my system may have been in balance on the collection of meds started for TLE 20 years ago and the Diabetes may have decrease nitric oxide and changed the balance. Many of the drugs I was given 20 years ago VPA, Selegiline increase NO, and propranolol was of course blocking the highs of the HR. link to Rituximab story, with full article at bottom link here... http://thoughtsaboutme.com/2011/10/20/norwegian-rituxan-study-published/

The Acylcarnitine profile seems to have had some impact on the genetics doctor.. I alwyas wonderes as my CK (CreatinePhosphokinase) has always been 2-4 times normal, which is not alot compared to some muscle disorders etc. but is clearly not normal. I am really hoping someone can tell me about these skin biopsy and in vitro fatty acid oxidation probe.

Ramakentesh, It seems like their are alot of possibilities. I guess that is why I like the flow divisions that Dr. Stewart is using. Their is not a lot of overlap in the flow categories if you look at the charts. Now that in no way implies that the etiolgy is the same, but it might help point a direction towards treatment. Also, it seems like more than one type of treatment might be applicable. As an example in one person if an autoimmune response of the body was being mounted against the ACE2 in a given person, and that resulted in increased Angiotensin II and that resulted in decreased nitric oxide and that resulted in increased microvascular resistance and that resulted in a sympathetic increase to provide enough blood to the brain, and that resulted in an increase HR and BP there might be several ways you could treat. B-blocker might slow the HR. ARB might increase nitric oxide, decrease peripheral resistance, and thereby decrease sympathetic activity ( if it is a compensatory action in that case ) and lower the heart rate. Yet the best way might be to block the immune system or response that is attacking the ACE2, via something like Rituximab, as they recently had success with CFS patients with. ( I do not know if they are using it with POTS ) There are obviously a lot of possibilities, for types and etiology but it seems to me that narrowing down the type certainly helps in choosing treatments. I think there are likely to be many etiologies to the same damaged sytem with common pathways. But if I wanted to fix the spillway to a ****** up lake I would want to know if the problem was the water level was rising or falling as a start to figuring out what the spillway problem was.

I saw a mito. genetics doctor last spring due to elevated CK and ammonia, and slightly decreased free carnitine as well as mild elevations of short-chain fatty acids on acylcarnitine profile. I recently had another acylcarnitine profile, just before tilt test, that showed additional mild elevations of C-2, C-16, C16:1-hydroxy, C18, C18-hydroxy. I wrote to him and he suggested I may want to make an appointment and have a skin biopsy and in vitro fatty acid oxidation probe. Does anyone know anything about these things?? Any and all info appreciated.

was just posting on this in ( not sure if I should repost or link to say the same. I did both but let me know the correct form. ) as I am very interested in which type and how you tell if you can't have your "flow" type tested. In Topic: How Do You Know If U R Hyper Vs Hypo Pots Yesterday, 04:00 PM I am interested in whether I have Hyperadrenergic POTS as Dr. Stewart in "Primer on the Autonomic Nervous System" edited by Italo Biaggioni, David W. Robertson, Geoffrey Burnstock, Phillip A. Low, Julian F.R. Patonstates that "Low flow" POTS is similar to the "Hyperadrenergic" POTS originally proposed by Streeten. His research indicates that "low flow" POTS has reduced nitric oxide and that "regular flow" and "high flow" POTS have increased nitric oxide. Thus, if I have Low Flow POTS then treatments that increase nitric oxide such as Losartan ( via blocking Angiotensin 2 type 1 receptors ) and Vitamin C, among many other possibilities might help me. If I have one of the other types of POTS they might make me worse. Now Dr. Stewart himself writes that " these categories comprise fuzzy sets " however, if I wait till they figure it out I will not be well for a long time and I am sure many people on this site also see it as taking a best guess with their doctor. Using this same reference I would note that Low Flow patients frequently have increased Angiotensin 2, have a higher HR, including resting than the other two types. ( one of his studies showed 85-90 average supine ), "generalized pallor, cool skin, and other findings suggesting circulatory insufficiency" "There is a marked female gender preference" ( I am male but that is not an exclusion. ) " 'There is also an inverse relationship with body mass index" " These patients often have increased upright concentrations of NE" In http://www.stars-us....roof%20copy.pdf Dr. Blair Grubbs 2011 article refering to 29 Hyperadrenergic patients he notes " Patients were diagnosed as having the hyperadrenergic form based on an increase in their systolic blood pressure of >10mmHg during the HUTT (2) with concomitant tachycardia or their serum catecholamine levels (serum norepinephnrine level 600 pg/mL) upon standing. My cardio said my blood pressure was increased 10 on tilt but it really stays about the same on average and bounces alot. I would not say I have general Pallor but definately have cold hands and feet and Raynoud's syndrome. I have a BMI of 23, and Type 2 diabetes which decreases NO. I have a high lying HR ( 85-105 ) and standing bounces to 156 and as low as lying but always goes over 130 off meds. High dose ( 140mg ) propranolol does not completely lower HR. I am waiting on Free Catecholamines sitting and standing, Angiotensin 2 Renin, and Aldosterone. ( They were unfortunately done back on high dose B-blocker. ) I think I have low flow, hyperadrenergic, POTS but am not certain by any means.

Ramakentesh, I take carnitor the prescription form of L-Carnitine liquid 30ml (2 tbsp.)=3000mg. It is supposed to be good for TLE and my TLE doctor measured my free carnitine which was low. I have taken it daily for some time and can not really tell that it does anything. It has no side effects for me.

Rama, I was told that Licorice increase NO also. What dose of Inderal do you take? Do you have to take it frequently?

Naomi, I am not sure it is just a helping or not helping POTS thing as it has multiple effects. For me the NO ( nitric oxide ) increase might be good. The Epi ( Epinephrine) and NE (Norepinephrine ) could be good or bad. For someone with a different subset of POTS that affect might be different. I am glad you got to enjoy some sun though. Not sure on the vitamin D. I suspect that sunlight feels good partially because it speeds the heart a little and relaxes the vessals sending more blood in a "normal" ( meaning without POTS ) person. For the rest of us its "potluck" What is strange for me is having spent countless hours in the bright sun over the past 2 years ( as it relieved my symptoms ) why did my vitamin D level just come back at 30.7 ( barely low normal ) ? This is why my picture is of the sunrise. I realize this sun relieving POTS thing is wierd but it is true.

Hi all, Issie just aked if I would come to this thread to explain some sunlight connections I have come across. Regarding the above I have heard of the "Marshall Protocol" if this isthe same guy, and would have to agree with Rama's opinion, if it is that guy that he is a bit of a maverick. I was also recently referred to a guy who's entire site is about deficiency of NO which he feels is a cause of Autism and many things. One thing I learned is nitrates are converted to nitrites via bacteria in the mouth and stomach. ( For example in spinach or Issies favorite beet juice ) The sun seems to increase NE and Epi via the iPRGc cells in the eye which connect to the SCN of the hypothalmus. Epi has a circadian rythm without the sun, but NE does not. Secondly it affects vitamin D via longer term exposure to the skin. This affects and is affected by the Renin-Angiotensin-Aldosterone system. Third sunlight causes a rapid increase in NO which is at least partially mediated through infared or heat on the skin and possibly tetrahydrobiopterin. I developed dizziness and brain fog type symptoms 2 years ago while already on Propranolol, that were relieved by direct sunlight, and worse on cloudy days. I have done an incredible amount of research on sunlight and its effects. As Issie was asking about my profile and the sun relieving my symptoms that is why I noted some of these things. I am not sure if they are of any help to this thread but hope so. The sun does not have the same effect on me now, as I have been off Propranolol for some time diagnosed with POTS and am back on Propranolol. ( I am guessing up and downregulation of B1 & B2 receptors has changed my baseline. )

I am interested in whether I have Hyperadrenergic POTS as Dr. Stewart in "Primer on the Autonomic Nervous System" edited by Italo Biaggioni, David W. Robertson, Geoffrey Burnstock, Phillip A. Low, Julian F.R. Paton states that "Low flow" POTS is similar to the "Hyperadrenergic" POTS originally proposed by Streeten. His research indicates that "low flow" POTS has reduced nitric oxide and that "regular flow" and "high flow" POTS have increased nitric oxide. Thus, if I have Low Flow POTS then treatments that increase nitric oxide such as Losartan ( via blocking Angiotensin 2 type 1 receptors ) and Vitamin C, among many other possibilities might help me. If I have one of the other types of POTS they might make me worse. Now Dr. Stewart himself writes that " these categories comprise fuzzy sets " however, if I wait till they figure it out I will not be well for a long time and I am sure many people on this site also see it as taking a best guess with their doctor. Using this same reference I would note that Low Flow patients frequently have increased Angiotensin 2, have a higher HR, including resting than the other two types. ( one of his studies showed 85-90 average supine ), "generalized pallor, cool skin, and other findings suggesting circulatory insufficiency" "There is a marked female gender preference" ( I am male but that is not an exclusion. ) " 'There is also an inverse relationship with body mass index" " These patients often have increased upright concentrations of NE" In http://www.stars-us.org/files/file/Clinical%20papers/110912-Hyper-POTS%20Proof%20copy.pdf Dr. Blair Grubbs 2011 article refering to 29 Hyperadrenergic patients he notes " Patients were diagnosed as having the hyperadrenergic form based on an increase in their systolic blood pressure of >10mmHg during the HUTT (2) with concomitant tachycardia or their serum catecholamine levels (serum norepinephnrine level 600 pg/mL) upon standing. My cardio said my blood pressure was increased 10 on tilt but it really stays about the same on average and bounces alot. I would not say I have general Pallor but definately have cold hands and feet and Raynoud's syndrome. I have a BMI of 23, and Type 2 diabetes which decreases NO. I have a high lying HR ( 85-105 ) and standing bounces to 156 and as low as lying but always goes over 130 off meds. High dose ( 140mg ) propranolol does not completely lower HR. I am waiting on Free Catecholamines sitting and standing, Angiotensin 2 Renin, and Aldosterone. ( They were unfortunately done back on high dose B-blocker. ) I think I have low flow, hyperadrenergic, POTS but am not certain by any means.

It is easy to see why your name is forevertired if HR is running over 100 when sleeping ( or trying ) I am new to the forum. It is nice to meet you. I hope they have some suggestions. My HR runs 85-105 lying off meds but I am back on whopping dose of Inderal LA ( 80mg AM & 60mg PM ) It is supposed to be once daily but it lowers my HR a few hours after I take it and then HR slowly rises back till 110-120 standing before PM dose which lowers it again so I request BID. I have trouble sleeping, especially off Propranolol and have tried several things. I asked the cardio who treats POTS what he recommends but he said see the sleep team. Obviously that is what you have done. Klonopin .75 seems to be helping. Benadryl 25 seemed to slow HR and make me sleep but not feel good when awake. Ambien 5-10 works for me for short time, not alway full night. I do not like being on these meds and hope that getting better control of the Hyperadrenergic POTS will help with the sleep but in the meantime I am taking the Klonopin.