Nitric Oxide-Different Reactions To Medicines...vasoconstriction And Vasodilation

[RichGotsPots]

interesting to note that endothelium regulates this and as noted in Wikipedia certain drugs that are Cholinergic may dilate or constricted depending whether the endothelium is damaged.

How many of you know if your endothelium is damaged? BTW is regulates Nitric Oxide...

This may be one reason some of us react differently to certain meds even if we have the same type of POTS...

Regulation of vascular resistance

There are many factors that alter the vascular resistance. Many of the platelet-derived substances, including serotonin, are vasodilatory when the endothelium is intact and are vasoconstrictive when the endothelium is damaged.

Cholinergic stimulation causes release of endothelium-derived relaxing factor (EDRF) (later it was discovered that EDRF was nitric oxide) from intact endothelium, causing vasodilation. If the endothelium is damaged, cholinergic stimulation causes vasoconstriction.

A cholinergic drug, also known as a cholinergic agent, cholinergic agonist,^[4] or a parasympathomimetic drug,^[5] is any drug that functions to enhance the effects mediated byacetylcholine in the central nervous system, the peripheral nervous system, or both. These include acetylcholine's precursors and cofactors, acetylcholine receptoragonists,acetylcholinesterase inhibitors and cholinergic enzymes:

• Acetylcholine receptor agonists
  • Alvameline
    
  • Muscarine (muscarinic receptors)
    
  • Nicotine (nicotinic receptors)
    
  • Pilocarpine (M₃ receptors)
    
  • Suxamethonium (muscle type receptors)
    

• Acetylcholine receptor antagonists
  • Scopolamine
    
  • Dicycloverine
    
  • Tolterodine
    
  • Oxybutynin
    
  • Ipratropium
    
  • Mamba Toxin (MT₇)
    
  • Pirenzepine
    
  • Telenzepine
    

• Acetylcholinesterase inhibitors (abbreviated AChEIs)
  • Donepezil
    
  • Galantamine
    
  • Huperzine A
    
  • Neostigmine
    
  • Physostigmine
    
  • Rivastigmine
    

[anna]

So Endothelium cell's do seem to be responsible for a lot of things, oh more reading, my head hurts!

[ramakentesh]

Endothelial function is being evaluated right now in POTS by Vandy. This is because in many cases local factors - that is local endothelial factors, rather than absolute neurovascular problems have been implicated at least in a subset of POTS.

For a start, a major subset of POTS patients have elevated angiotensin II. This would cause an imbalance in the nitric oxide/superoxide ratio resulting in reduced nitric oxide bioavailability and increased ROS activity (increased endothelial inflammatory markers such as substance P, Calcitonin Gene Related Peptide and perhaps Assymetric Dimethylarginine and increased signs of oxidisive stress).

The endothelium in Low Flow POTS that is related to elevated Angiotensin II is very similar to that in heart failure.

Nitric oxide is involved in vasodilation both at the neuronal and endothelial level and in Low Flow POTS its still unclear which is abnormally low. On the other hand in normal flow POTS there seems to be an excess of nitric oxide in the splanchnic (stomach) circulation causing inappropriate blood flow in that region and symptoms of POTS.

The endothelium is highly complicated. There is a myriad of vasodilators and many but not all rely ultimately on nitric oxide to vasodilate (some utilise potassium channels, some hydrogen sulfide which is another vasoactive molecule) including histamine.

Acetylcholine related vasodilation isnt really the best indicator of endothelium health. Flow measurements and vasodilatory responses under specific nitric oxide competitors and donors are often use to evaluate endothelial responses. There are also the newly described nitrergic nerves in the parasympathetic system that are of increasing interest to cardiovascular research.

In CFS patients seemed to have increased vasodilatory responses to acetylcholine specific to the microvascular, implicating hydrogen sulfide rather than nitric oxide.

[RichGotsPots]

Very interesting to say the least. How can i get my hands on the Vandy research? This all follows my theory which ultimately I tie to localized organ BP issues. There are so many factors and each act as a domino, the last domino is the local BP variations causing chaos. The question is diagnosing the BP variation locally and a similar way that we can check for postural tachycardia variations or how posteral hypo/hypertesion can be seen. Most tests are not taking in a Tilt environment especially outside of POTS centers..

For example I think with your main symptom being dizziness you need to be tested for intracranial hypo/hypertension by a Neurologist in this specialty. That isn't going to tell you why you have it if it's secondary but at least you can start a treatment to control it... if that's what you have. But again it might only show up while in tilt positions

[ramakentesh]

I recommend that you review the research so you know what has been implicated and excluded from the picture in POTS. I can understand you want to work it out but without the ability to test your hypothesis and without considering current medical opinion you're pretty much wasting your time, in my opinion.

I don't think my dizziness has anything to do with intercranial pressure. Can you refer me to reputable research where this was tested or implicated specifically in POTS patients?

[RichGotsPots]

I'm working on my own symptoms start googling, begin with this article http://www.nature.com/hr/journal/v33/n12/full/hr2010208a.html. No affects BP and yes on the local level not just systemically..

Baroreflex sensitivity is disturbed in many people with cardiovascular diseases such as hypertension. Brain deficiency of nitric oxide (NO), which is synthesized by NO synthase (NOS) in the citrulline–NO cycle (with argininosuccinate synthase (***) activity being the rate-limiting step), contributes to impaired baroreflex. We recently showed that a decapeptide isolated from Bothrops jararaca snake venom, denoted Bj-PRO-10c, exerts powerful and sustained antihypertensive activity. Bj-PRO-10c promoted vasodilatation dependent on the positive modulation of *** activity and NO production in the endothelium, and also acted on the central nervous system, inducing the release of GABA and glutamate, two important neurotransmitters in the regulation of autonomic systems. We evaluated baroreflex function using the regression line obtained by the best-fit points of measured heart rate (HR) and mean arterial pressure (MAP) data from spontaneously hypertensive rats (SHRs) treated with Bj-PRO-10c. We also investigated molecular mechanisms involved in this effect, both in vitro and in vivo. Bj-PRO-10c mediated an increase in baroreflex sensitivity and a decrease in MAP and HR. The effects exerted by the peptide include an increase in the gene expression of endothelial NOS and ***. Bj-PRO-10c-induced NO production depended on intracellular calcium fluxes and the activation..........

[issie]

Why would you presume to think that my dizziness has anything to do with intercranial pressure? can you refer me to any reputable research where this was tested or implicated specifically in POTS patients?

Rama,

There is a doctor who is looking at intercranial pressure and EDS. She thinks that part of our problems are related to the flow of fluid and lack of flow from the brain building up a pressure in our heads. Her name is Dr. Diania Driscoll and she has a government grant to do this study. She also has POTS and says there is a connection. I find her theories very interesting. She is trying to connect the dots and put the word out on this. She thinks that compression on the brain stem is causing allot of the issues and that if we get the fluids in the spinal cord to drain properly - then we won't have as many issues. She is an eye doctor and has noticed that there is increased pressure on the eyes because of this. I don't know if it's only those with EDS that have this problem or if it could be a problem with all POTS people. But, I'm staying tuned in on this idea.

Issie

[ramakentesh]

There are a myriad of doctors researching all manner of things in relation to CFS and POTS. the research on brain stem compression in relation to dysautonomia is sketchy at best and not widely accepted in the current viewpoints at least on POTS.