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Florinef at odds with BNP?

Sherlock

Boswellia for lungs and MC stabllizing
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To mention a thought which occurred to me after listening to Cheney's 2005 talk: he says that CFS problems arise from Diastolic Dysfunction (which itself arises from mito dysfunction). When heart muscle gets over-taxed, it releases BNP (called Brain Natriuretic Peptide, which was originally found in tiny amount in the brain, but is now well-known to be a marker for heart failure).

BNP is a diuretic, so lessening of blood volume eases the workload of the heart (also causing polyuria). However, in some people, that results in Orthostatic Intolerance of various types. While Florinef can help with the OI, it unfortunately might also counteract the body's effort to try and protect the heart. I don't know if Cheney mentions that, or even if the concern is valid. It's just a thought.
 

alex3619

Senior Member
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Interesting Sherlock. :) Is there any evidence that BNP is routinely elevated in ME or CFS? Are there similar chemicals that could be raised (or lowered) instead and have a similar impact? This might include any axis that BNP might work with. I have never really read much on BNP, only the basics, so I do not know what else is involved.
 

Sparrow

Senior Member
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691
Location
Canada
This would explain well why I tend to get more desperately thirsty and why it feels like fluids go right through me when I'm feeling more crashy.

I often wonder about things like this. I'm never sure with any of this stuff whether a symptom is the result of something wrong that should be forcibly corrected, or whether a symptom is something the body is doing in an attempt to protect itself and should be left alone.
 

Sherlock

Boswellia for lungs and MC stabllizing
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This would explain well why I tend to get more desperately thirsty and why it feels like fluids go right through me when I'm feeling more crashy.
Amen to that, Sparrow. I am the same! It gets to the point of being ridiculous, those powerful diuretic episodes, whenever I get sick. So at one time I looked into symptoms that are experienced by people who take synthetic interferon (e.g. in Hep C). Polyuria was there (along with the burning eyes that I experience). So I thought that INF was the cause. But then I looked into histamine, and found that histamine can cause polyuria also. Plus, diphenhydramine/Benadryl counteracts the polyuria very well.

(Meanwhile, if it's nocturia instead of polyuria, then that can be from fluids that were pooling in the legs being returned to circulation from lying down - then filtered out by the kidneys.)

Now here's a catch: I used to get the same polyuria from candida spells, long before my post-viral CFS. I get it again now from a common cold, or from candida.

I often wonder about things like this. I'm never sure with any of this stuff whether a symptom is the result of something wrong that should be forcibly corrected, or whether a symptom is something the body is doing in an attempt to protect itself and should be left alone.
You bet. It's like people wrongly taking a Tylenol for a fever - which is simply counteracting what the body wants to do to fight some infection. Then again, if the fever gets dangerously high (106F ?), you probably should lower it with a drug or some other measure like ice. Probably.
 

xks201

Senior Member
Messages
740
Can't rule out vasopressin deficiency either. One study showed blood volume was not commensurate with AVP output even though these patients did have some AVP production.
 

Emootje

Senior Member
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356
Location
The Netherlands
I've been tested for BNP (brain natriuretic peptides) and ANP (atrial natriuretic peptides). BNP was normal and ANP was 3 times the upper limit. ANP secretion is enhanced by inflammation (see this and this video) which could explain my abnormal ANP and Sherlock's natiuretic effect during a candida or a common cold infection. Intravenous injection of LPS in rodents causes a rise in plasma ANP concentrations and a reduction in plasma volume. This is also true in humans with endotoxic shock or leaky gut, in whom plasma ANP levels are significantly elevated. So I think the big question remains why we are inflamed an how do we prevent it?
 

Sherlock

Boswellia for lungs and MC stabllizing
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k8518704 USA
Is there any evidence that BNP is routinely elevated in ME or CFS?
I, for one, don't know. But my guess is that it's not routinely tested anyway.

Are there similar chemicals that could be raised (or lowered) instead and have a similar impact? This might include any axis that BNP might work with. I have never really read much on BNP, only the basics, so I do not know what else is involved.
For diuresis? Let's see... there's interferon, also probably histamine (e.g., polyuria occurs in anaphylaxis), RickVanK talks about Diabetes Insipidus as being the cause (the non-blood-sugar kind) but I don't know the mechanism in DI.
 

Sherlock

Boswellia for lungs and MC stabllizing
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Location
k8518704 USA

I've been tested for BNP (brain natriuretic peptides) and ANP (atrial natriuretic peptides). BNP was normal and ANP was 3 times the upper limit. ANP secretion is enhanced by inflammation (see this and this video) which could explain my abnormal ANP and Sherlock's natiuretic effect during a candida or a common cold infection. Intravenous injection of LPS in rodents causes a rise in plasma ANP concentrations and a reduction in plasma volume. This is also true in humans with endotoxic shock or leaky gut, in whom plasma ANP levels are significantly elevated. So I think the big question remains why we are inflamed an how do we prevent it?
Emootje, you seem to me to be very correct in pointing to elevated natriuretic peptides being more likely caused by inflammation/infection, rather than by occult heart failure, in CFS. (Though I suppose that a Cheney-type of view could still say that ventricular diastolic weakness/dysfunction could lead to compensation by the atrium... say, the left ventricle doesn't expand enough in diastole, so the left atrium pumps harder to fill the left ventricle and make it expand - like blowing up a balloon with liquid... therefore provoking ANP release).

So, why would an infection result in diuresis? What's the advantage? It might be if the lungs are involved in the infection. Reducing pulmonary pressure might reduce lung congestion - so less liquid is being forced into the lung alveolas and getting in the way of breathing. It does seem that BNP is used as a prognostic indicator in COPD (Chronic Obstructive Pulmonary Disease). Also in pneumonia:
"Utility of brain natriuretic peptide as prognostic marker in community-acquired pneumonia and chronic obstructive pulmonary disease exacerbation patients presenting to the emergency department."
http://www.ncbi.nlm.nih.gov/pubmed/22212162

The [Community-acquired pneumonia] patients had significantly higher mean BNP values in comparison to acute bronchitis patients (127.2 Vs 45.9 pg/mL; p=0.003)

Or, looking at it the other way around:
"Intravenous diuretic and vasodilator therapy reduce plasma brain natriuretic peptide levels in acute exacerbation of chronic obstructive pulmonary disease."
http://www.ncbi.nlm.nih.gov/pubmed/22394412

Maybe Pulmonary Hypertension is something to be looked into. It doesn't seem to be much discussed with regard to CFS, though merylg mentioned it in a recent SOB thread.

But all this could go round and round. E.g.
Plasma BNP levels were inversely associated with blood haemoglobin levels.
"What factors are associated with high plasma B-type natriuretic peptide levels in a general Japanese population?"
http://www.nature.com/jhh/journal/v19/n2/full/1001792a.html


---


Here's another wrinkle of naming: C Natriuretic Peptide is not natriuretic... go figure. But apparently it is a vasodilator, as are the other two (A and B).
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
I've been tested for BNP (brain natriuretic peptides) and ANP (atrial natriuretic peptides). BNP was normal and ANP was 3 times the upper limit. ANP secretion is enhanced by inflammation (see this and this video) which could explain my abnormal ANP and Sherlock's natiuretic effect during a candida or a common cold infection. Intravenous injection of LPS in rodents causes a rise in plasma ANP concentrations and a reduction in plasma volume. This is also true in humans with endotoxic shock or leaky gut, in whom plasma ANP levels are significantly elevated. So I think the big question remains why we are inflamed an how do we prevent it?

The evidence is strong that many to most of us have high serum LPS. This has lots of secondary consequences. It might be worth looking more closely at ANP.
 

Sherlock

Boswellia for lungs and MC stabllizing
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1,287
Location
k8518704 USA
...and following some studies cited in Emootje's video: lung infection and/or hypoxia results in release of endothelin. Why does the system want a pressor in that situation? Well, it would seem logical that hypoxia might be reversed with a higher BP. But then again, endothelin leads to NP induced vasodilation and diuresis. Is it another Yin/Yang balancing act? In fact, there is a factor with that name: "Endothelin-Stimulated Human B-Type Natriuretic Peptide Gene Expression Is Mediated by Yin Yang 1 in Association With Histone Deacetylase 2 http://hyper.ahajournals.org/content/53/3/549.long

My first symptoms (post-virus) were sudden onset hypertension with orthostatic hypotension. Why was my balancing act so disrupted, when that of most people isn't so disrupted? Maybe because of my excess histamine. Looking to round up the usual suspects, the Mast cells, there they are:
"Response of cardiac mast cells to atrial natriuretic peptide"
http://ajpheart.physiology.org/content/293/2/H1216.full 2007
Forget the cardiac mast cells, it is the peritoneal mast cells that degranulate mightily from ANP (Figure 1). I'd guess that other MCs also are sensitive to ANP, while cardiac ANPs are the exception.

Possible strategies: inhibit infections, inhibit mast cells, uses some enzyme to metabolize NPs, use some NP blocker

Big worrisome side note: this chain of events involves activation of MMPs (Matrix MetalloProteinases). That AJP study will require some studying.
 

Emootje

Senior Member
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Location
The Netherlands
Yes endothelin-1 plays a major role in hypoxia stimulated ANP release. In isolated perfused rat atria, anoxia results in a dramatic increase in ANP secretion and this is almost entirely blocked by a endothelin-1 receptor antagonist. COPD patients with a PaO2 of 60 mmHg or higher have almost normal plasma natriuretic peptide levels and patients with a PaO2 less than 60 mmHg have increased levels of plasma ANP and BNP suggesting that the hypoxia is responsible for the rise in ANP and BNP. Plasma concentrations of atrial, brain, and C-type natriuretic peptides and endothelin-1 in patients with chronic respiratory diseases

Besides hypoxia there are many other factors that increase the secretion of endothelin-1 (and thus ANP secretion):

et-1.JPG

Why the body response with the ET-1 vasoconstrictor in stress situations I do not understand, it seems to do more harm than good.

I simply don't know if diastolic dysfunction stimulates ANP and/or BNP. If I recall correctly this diastolic dysfunction is according to Cheney due to ATP depletion.
An alternative explanation for Cheney's diastolic dysfunction findings is that this dysfunction is due to volume depletion:

"Reduced plasma volume may contribute to reduced ventricular filling, stroke volume, and cardiac output and increased blood viscosity. Consistent with reduced preload, transmitral Doppler studies have revealed reduced E-to-A wave ratio and prolonged deceleration time in adult patients with cyanotic congenital heart disease, findings that are very similar to those of the present study. When cardiac output is reduced in adults with cyanotic congenital heart disease, it is because of volume depletion rather than ventricular dysfunction, unlike patients with heart failure"
Increased Atrial and Brain Natriuretic Peptides in Adults With Cyanotic Congenital Heart Disease

I think that the best strategy is to eliminate the source of inflammation (infection, leaky gut, allergies, autoimmune diseases, stress, hypoxia, sugar intake, pollution). Natriuretic peptides protect the heart at the expense of perfusion, so if you lower the NP's the heart will pay the price. Best is to eliminate the source.
 

taniaaust1

Senior Member
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13,054
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Sth Australia
I think its risky to assume something goes on with BNP in ME/CFS when BNP being high hasnt been found in any ME/CFS studies. There can be so many other reasons for polyuria in ME/CFS.

One thing I do know that orthostatic hypertension puts one at risk of life threatening other things eg strokes.. so hence not treating it, whether its by correcting low blood volume or whatever, is probably more dangerous then worrying about BNP esp when no studies have shown it to be high in us.

Also its a bit thing to be able to live a better life when one has a symptom which is treatable and hence then allows one to be living a better life (for some, even to go back to work). Thou I guess its a choice we all make.. do we have treatment which may carry risks or do we just live with the symptoms and live a life which isnt as good as it possibly could be.
 

Sherlock

Boswellia for lungs and MC stabllizing
Messages
1,287
Location
k8518704 USA
I think that the best strategy is to eliminate the source of inflammation (infection, leaky gut, allergies, autoimmune diseases, stress, hypoxia, sugar intake, pollution). Natriuretic peptides protect the heart at the expense of perfusion, so if you lower the NP's the heart will pay the price. Best is to eliminate the source.
Taking the liberty to adjust that to chronic inflammation, which I assume you mean anyway, then yes that's best - if possible.

But the other very real possibility as to the cause of chronic inflammation is some self-sustaining, pathological loop - maybe caused in most cases by some SNP. My impression is that's generally under-investigated. You might have read the recent etanercept thread, with the video of the guy who had crippling radicular sciatica which resolved in minutes via antagonizing TNF.

Here is a pertinent quote regarding TNF and psoriasis:
Overproduction of inflammatory mediators, such as tumor necrosis factor-alpha (TNF-alpha) and IFN-gamma, results in a self-sustaining inflammatory cascade...
http://www.ncbi.nlm.nih.gov/pubmed/17502868 2007

And btw, my guess is that rapid effects from RTX occur in a similar theme, via disruption of signalling.
 

Sherlock

Boswellia for lungs and MC stabllizing
Messages
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Location
k8518704 USA
I think its risky to assume something goes on with BNP in ME/CFS when BNP being high hasnt been found in any ME/CFS studies. There can be so many other reasons for polyuria in ME/CFS.
Are NPs routinely or regularly tested for in CFS, Tania? I had taken a quick look before starting this thread, but didn't see that (and not also at e.g. labtestsonline.org)

I'd guess there are several elevated endogenous diuretics involved in CFS polyuria - as with everything, CFS seems to touch on all the redundant mechanisms that nature has provided.

As for myself, I'm back to thinking in terms of histamine (and interferons) as the main cause of most everything in me. As I ramp up my quercertin intake, polyuria seems lessened... except in the first hour after getting up, which seems like the opposite of nocturia.

Hey, lookee here :) Having happened to use Bing to search just now for--> bnp cfs
this thread is result #2
http://www.bing.com/search?q=bnp cfs&FORM=IE8SRC


Annnnnd it's #1 at privacy-invading google: http://www.google.com/#hl=en&q=bnp cfs

The topic must be not widely discussed :)
 

xks201

Senior Member
Messages
740
DI is tricky though if you have potential low aldosterone because taking desmopressin is going to raise potassium and dilute your sodium more. lol I know this because I take both drugs. And to make matters worse the water deprivation test for low ADH output is beyond worthless unless you are braindead and produce absolutely no ADH, which studies have shown is not the case in a lot of CFS people who have PARTIAL DI.
 

alex3619

Senior Member
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13,810
Location
Logan, Queensland, Australia
Hi Little Bluestem, I have a pending blog which is just a long glossary of terms. I should move it up as I have been asked about LPS at least three times this week alone. LPS is lipopolysaccharide, a toxic chemical on the outside of many bacteria, including gut bacteria. Too much in the blood induces shock. Smaller amounts cause all sorts of physiological changes which I am trying to figure out - and may be a big factor in causing ME, or not.Bye, Alex
 

Emootje

Senior Member
Messages
356
Location
The Netherlands
Taking the liberty to adjust that to chronic inflammation, which I assume you mean anyway, then yes that's best - if possible.
Yep I meant chronic inflammation. By the way, anti-inflammatory herbs are counterproductive for me. I guess I need some inflammation to control my infections...
 

Ema

Senior Member
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Location
Midwest USA
This is a REALLY old thread but now we have confirmation in the research that BNP is elevated in MECFS...elevated BNP inhibits aldosterone secretion and promotes salt wasting and hypovolemia and inhibits autonomic outflow at the brainstem.

So the question remains...is the elevated BNP protective of the heart?

Or just collateral damage, that might be helped by replacing the aldosterone that is suppressed with Florinef?