Could aldosterone gone bad be the cause of ccsvi and ms?

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Re: Could aldosterone gone bad be the cause of ccsvi and ms?

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1eye wrote:I believe I read that LDN stimulates FSH and LH. Maybe that is connected with its effectiveness when precisely timed in synchrony with other circadian cycles. Maybe circadian release of aldosterone can get out of whack too?
Yes, LDN does stimultate LH production. Circadian cycles? Oh boy. My poor brain. lol I could totally be missing your point here because circadian rhythms are not something with which I am familiar.

http://www.endotext.org/adrenal/adrenal ... rame27.htm
Circadian variability is observed in all adrenal hormones. Aldosterone levels are elevated during the sleep period (correlated with plasma renin activity), whereas pulse amplitude and frequency are reduced during waking periods (correlated with cortisol) (6). This pattern suggests that aldosterone secretion is under the influence of the renin-angiotensin-aldosterone system during sleep, and under the influence of the adrenocorticotropic system during wakefulness (Figure 1).

Image
I guess, assuming that LDN has an effect on aldosterone levels via LH-progesterone pathway, both timing and dosage of LDN would be critical to optimizing it's impact on aldosterone production. LDN would have to be taken at a time that would allow for progesterone increase (how long does it take to go from LH to progesterone increase?) just about the time aldosterone's circadian peak comes along (just before sleep). I think you also have to find the perfect dosage because too much progesterone feeds the aldosterone, rather than blocks it. I wonder if that's why people have to fiddle with their LDN dosage so much.

Tell me more about this circadian cycle getting out of whack...
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Re: Could aldosterone gone bad be the cause of ccsvi and ms?

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MarkW wrote:Anonymoose asks: Could aldosterone gone bad be the cause of ccsvi and ms?
Highly unlikely that MS has one cause. A factor in MS in some people is
possible as there appears to be many factors involved in MS.
MarkW
You don't find it odd that so many of the MS related factors/cofactors/mysteriously successful treatments can be associated with aldosterone? If there are factors I am missing please do point them out because I want to know if aldosterone is the cause or not.
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Re: Could aldosterone gone bad be the cause of ccsvi and ms?

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Yes, LDN does stimultate LH production. Circadian cycles? Oh boy. My poor brain. lol I could totally be missing your point here because circadian rhythms are not something with which I am familiar.
The late Dr. Bihari theorized (this is my own understanding) that the short-lived opioid block of LDN, taken at bedtime, when endorphin production is at a low point, would make the next day's high point a bit higher because production would rev up in compensation, and that regular use would train you to produce more.

Apparently people with cancers, HIV, and MS have chronically low endorphin production. Perhaps the same kind of training effect is seen with other hormones. I don't know. Neither can I guess why it would affect venous drainage, steroid production, or the endothelium or BBB. Sorry. Not very knowledgeable in this stuff.
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Re: Could aldosterone gone bad be the cause of ccsvi and ms?

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http://cardiovascres.oxfordjournals.org ... 2/318.full
The role of natriuretic peptides in cardioprotection
Abstract

Atrial natriuretic peptide (ANP) and brain (B-type) natriuretic peptide (BNP) are circulating hormones of cardiac origin that play an important role in the regulation of intravascular blood volume and vascular tone. The plasma concentrations of ANP and BNP are elevated in heart failure, and they are considered to compensate for heart failure because of their diuretic, natriuretic, and vasodilating actions and inhibitory effects on renin and aldosterone secretion. Evidence is also accumulating from recent work that ANP and BNP exert their cardioprotective functions not only as circulating hormones but also as local autocrine and/or paracrine factors. In studies using cultured neonatal myocytes and fibroblasts, exogenous administration of both ANP and ANP antagonists demonstrated that ANP has antihypertrophic and antifibrotic functions. Corroborating these in vitro results, mice lacking natriuretic receptor-A (NPR-A), the receptor for ANP and BNP, develop cardiac hypertrophy and fibrosis independent of their blood pressure. Recent studies also suggest that the intracardiac natriuretic peptides/cGMP system plays a counter-regulatory role against the intracardiac renin–angiotensin–aldosterone system and TGF-beta mediated pathway. In a clinical setting, human recombinant ANP and BNP may be used for a therapy of heart failure; however, further evaluation is required in the future.
http://endo.endojournals.org/content/129/2/801.short
Suppression of Luteinizing Hormone Secretion by Atrial and Brain Natriuretic Peptides in Ovariectomized Rats*

JIN ZHANG, BASIL HO YUEN, W. DAVID CURRIE and PETER C. K. LEUNG†
- Author Affiliations Department of Obstetrics and Gynecology, University of British Columbia, Grace Hospital, Vancouver, British Columbia V6H 3V5 Canada
Abstract

Brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) are present in brain regions regulating LH secretion. Similarities in the molecular structure of these peptides suggest similar physiological function within the brain. This study examined the effects of centrally administered BNP and ANP on LH secretion in mature ovariectomized (OVX) rats. Intracerebroventricular (icv) administration of 2 nmol ANP or BNP decreased mean plasma LH concentration and LH pulse amplitude (P < 0.05 for ANP; P < 0.01 for BNP; n = 8/group) and frequency (P < 0.01 for ANP and BNP). LH secretion was not affected by ANP or BNP at a lower concentration (0.2 nmol, icv; P > 0.05; n = 8/group). It was concluded that ANP and BNP may be involved in central regulation of LH secretion.

Mechanisms possibly involved in suppression of LH secretion by ANP and BNP were also examined. OVX rats were treated with an opioid antagonist, naloxone (0.5 mg, iv), 45, 75, and 105 min after ANP or BNP (2 nmol, icv). Naloxone eliminated suppression of mean plasma LH concentration and LH pulse amplitude by 2 nmol ANP and BNP (P < 0.05; n = 7/group). OVX rats were treated with a dopamine antagonist, pimozide (0.6 mg/kg, sc), 90 min before treatment with ANP or BNP (2 nmol, icv). Pimozide pretreatment blocked suppression of LH secretion by ANP or BNP (P < 0.05; n = 9/group). Naloxone alone did not affect LH secretion (P > 0.05; n = 5). It was concluded that components of ANP and BNP suppression of LH secretion may depend upon opioid and dopamine activity.
So, the ANP/BNP (which inhibit aldosterone) response to counter RAAS results in the inhibition of LH and downstream progesterone and dihydrotestosterone (which also inhibits aldosterone). Naltrexone would remedy the LH inhibition...not sure if helminth inspired LH increase would work. Will have to read through helminths again.

I wonder if that doesn't create a viscous cycle. Aldosterone burst, ANP/BNP response, reduced progesterone and dihydrotestosterone to block/inhibit aldosterone, ANP/BNP response, and on and on.
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Re: Could aldosterone gone bad be the cause of ccsvi and ms?

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hee hee @ viscous cycle.. given the context, it kinda works ;)
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Re: Could aldosterone gone bad be the cause of ccsvi and ms?

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jimmylegs wrote:hee hee @ viscous cycle.. given the context, it kinda works ;)
Doh! Vicious. I meant vicious! Lol.

I ewes too bee a gud speler.
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Re: Could aldosterone gone bad be the cause of ccsvi and ms?

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lol :D
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Re: Could aldosterone gone bad be the cause of ccsvi and ms?

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Having spent time studying negative feedback control systems, and knowing that some of these hormones participate in classic negative feedback loops, which must be complex and finely balanced, the idea of chemically forcing the systems to do a particular thing which is not their normal function, seems fraught with danger. Stability of these systems is easily broken.

In particular, determining correct dosage and timing of any modifications to this chemistry is even more difficult to achieve because a lot of it depends on the individual. Also, translating from rat or mouse to human may not work at all. The side effects may make a lot of things impossible.

Be that as it may, it is interesting, isn't it? Keep on digging.
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Re: Could aldosterone gone bad be the cause of ccsvi and ms?

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1eye wrote:Having spent time studying negative feedback control systems, and knowing that some of these hormones participate in classic negative feedback loops, which must be complex and finely balanced, the idea of chemically forcing the systems to do a particular thing which is not their normal function, seems fraught with danger. Stability of these systems is easily broken.

In particular, determining correct dosage and timing of any modifications to this chemistry is even more difficult to achieve because a lot of it depends on the individual. Also, translating from rat or mouse to human may not work at all. The side effects may make a lot of things impossible.

Be that as it may, it is interesting, isn't it? Keep on digging.
Yes, it is horribly complex and beyond my grasp. That said, it seems like we influence these negative feedback loops whether we try to or not. What if it is a vicious cycle that we or an infection or something set off at one point in time? If we break the cycle, maybe our bodies will be able to reset. Eplerenone anyone? It's used quite often in cardiac/stroke patients to block aldosterone...risk being hyperkalcemia. Under doctor supervision, I'd say its worth a try.
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Re: Could aldosterone gone bad be the cause of ccsvi and ms?

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Living in Canada I have long since given up thinking an MD would ever be talked into doing anything experimental. The ethics and legalities are too fuzzy. I think an MD would only use him or her self as a subject, without an ethics board. If you are going to try eplerenone, you're on your own in this place.

A negative feedback control system is one that more accurately amplifies or reproduces, correcting errors by using the difference between the input and a reconstructed version based on the output. It is a specific technical name for such a system. People have a number of them, temperature control and endocrine production being two. I happen to think that the smooth muscle control of vascular diameter is an important often-overlooked one.

I still haven't seen a definitive statement about whether or not cerebral veins have a smooth muscle layer. Knowing that might be very important. Viscous (or vicious) cyles refers more to an unstable system, that has positive feedback and gain greater than 1, and is therefor running away and out of control.
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Re: Could aldosterone gone bad be the cause of ccsvi and ms?

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1eye wrote:Living in Canada I have long since given up thinking an MD would ever be talked into doing anything experimental.
Experimenting is all MDs *can* do with MS, eh? Though I would agree the vast majority are probably reluctant to attempt any "unapproved" experiments and if asked to do so, MDs in Canada might even tell you to "takeoff hosehead!" (thankfully, that is all the Canadian I know)
1eye wrote: I still haven't seen a definitive statement about whether or not cerebral veins have a smooth muscle layer. Knowing that might be very important. Viscous (or vicious) cyles refers more to an unstable system, that has positive feedback and gain greater than 1, and is therefor running away and out of control.
In your previous post you warned that attempting to alter the negative feedback loops could result in an unstable system. Could the negative feedback control system not go haywire, resulting in positive feedback?

Some cerebral veins have smooth muscle layers.
http://www.ncbi.nlm.nih.gov/books/NBK53086/
Cerebral veins are very thin-walled compared to arteries. The larger pial veins have circumferentially oriented smooth muscle that is not present in veins in the parenchyma. Unlike veins in the periphery, cerebral veins do not contain valves [9].
Ran into something about myogenic tone and aldosterone but will have to put it all together and post later.
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Re: Could aldosterone gone bad be the cause of ccsvi and ms?

Post by Cece »

Anonymoose wrote:
Cece wrote:How does hypertension damage valves? I would be interested in this.
Baroreflex tests, interesting. The narrowed veins have been shown in Zamboni's research to have abnormal levels of collagen. If the collagen stiffens the vein, that could make it more constricted? Sympathetic nervous system dysfunction is a possibility but it does not cause sudden cut-offs in the outflow. My own MRV shows pretty good-looking veins on both sides coming to a sudden stop where the valve abruptly blocked the flow. That's not a case of constriction throughout the vein, but singular outflow obstructions in each vein.
Hi CeCe,

Thanks for your interest and input. Here's a study done on hypertension and valve damage. Hopefully it will answer your question.

http://www.sciencedirect.com/science/ar ... 1404003830
Hypertension-induced venous valve remodeling ☆

Presented as a poster at the Fifteenth Annual Meeting of the American Venous Forum, Cancún, Mexico, Feb 20-23, 2003.
Shinya Takase, MDa,
Luigi Pascarella, MDb,
John J Bergan, MDb, , ,
Geert W Schmid-Schönbein, PhDa
Abstract

Introduction

In human beings, chronic venous insufficiency is linked to venous hypertension. This in turn is associated with venous valve incompetence. This study was designed to test the hypothesis that venous hypertension serves to initiate a process that results in the venous valve and venous wall damage observed in venous insufficiency.



Conclusion

This study indicates that acute venous hypertension is accompanied by significant venous distention and some valve damage as early as 3 weeks after fistula creation. Inflammatory markers appear, along with leukocyte infiltration and increased adhesion molecule expression. We could not detect significant enhancement of MMP levels or nuclear transcription factors NFκB. It is uncertain whether this lack of evidence may be partially due to the enhanced apoptosis in venous valves and vein wall. Further details of the inflammatory cascade during venous hypertension need to be studied to improve current interventions.
Incidentally, one of my previous posts included a review on a study that proved that aldosterone can cause vascular damage in the absence of hypertension. I assume that valves are included in "vascular." I could be wrong though....
An interesting thread. My only concern about this abstract is that it is talking about hypertension leading to venous valve incompetence. That is when the valve is weakened and fails to close. In CCSVI, the valve is quite the opposite: overly thickened and fails to open. It appears that Lyme disease can potentially cause a version of this (thickened valve leaflets that are wavy) but that the smooth nature of the thickened valve leaflets in MS suggests that they may be congenital abnormalities rather than the result of a disease process; the 'wavy' appearance of the Lyme thickened valve leaflets is what it would look like if it were the result of a disease process. I have to reread what you've posted about aldosterone to know how that might fit in.
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Re: Could aldosterone gone bad be the cause of ccsvi and ms?

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Cece wrote:An interesting thread. My only concern about this abstract is that it is talking about hypertension leading to venous valve incompetence. That is when the valve is weakened and fails to close. In CCSVI, the valve is quite the opposite: overly thickened and fails to open. It appears that Lyme disease can potentially cause a version of this (thickened valve leaflets that are wavy) but that the smooth nature of the thickened valve leaflets in MS suggests that they may be congenital abnormalities rather than the result of a disease process; the 'wavy' appearance of the Lyme thickened valve leaflets is what it would look like if it were the result of a disease process. I have to reread what you've posted about aldosterone to know how that might fit in.
Good point. Two possible explanations/theories that could tie aldosterone into the valve-MS theory are 1. Aldosterone might damage the valve through endothelial dysfunction sans hypertension. 2. Assuming the valve abnormality is congenital, a failure in the autoregulation of cerebral blood flow, which had previously compensated for valve abnormality, allows blood flow irregularities to damage and/or negatively affect brain function. It is possible that aldosterone could play a part in this failure. I need to research more and go to med school but don't have time today. :p
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Re: Could aldosterone gone bad be the cause of ccsvi and ms?

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In your previous post you warned that attempting to alter the negative feedback loops could result in an unstable system. Could the negative feedback control system not go haywire, resulting in positive feedback?
Yes. An example might be overheating that somehow results in constriction of blood vessels and/or more internally generated heat. If the feedback is positive, the output errors are added to the original stimulus rather than being subtracted from it. An example of the gain being greater than one might be a 1 degree external temperature change causing a 1.5 degree change in internal temperature. It can't end well if there is both positive feedback and gain greater than 1. It has nothing to do with any other meaning of the words positive and negative. It's really more of a directional thing, in the same sense as "upregulation" and "downregulation".
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Re: Could aldosterone gone bad be the cause of ccsvi and ms?

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1eye wrote:
In your previous post you warned that attempting to alter the negative feedback loops could result in an unstable system. Could the negative feedback control system not go haywire, resulting in positive feedback?
Yes. An example might be overheating that somehow results in constriction of blood vessels and/or more internally generated heat. If the feedback is positive, the output errors are added to the original stimulus rather than being subtracted from it. An example of the gain being greater than one might be a 1 degree external temperature change causing a 1.5 degree change in internal temperature. It can't end well if there is both positive feedback and gain greater than 1. It has nothing to do with any other meaning of the words positive and negative. It's really more of a directional thing, in the same sense as "upregulation" and "downregulation".
Wandering about I found this and thought you might be interested. I believe the negative feedback loops of which you speak refer to a desired condition of homeostasis. This paper discusses allostasis which I believe more accurately describes the body's way of handling things...the body does adjust its limits and responses based on changes in condition. I believe I had read of this in a study about brain ischemia recovery and change in autoregulatory management of cerebral pressure. I could be remembering incorrectly though as I am in the middle of a stupefying antibiotic pulse.
http://www.sciencedirect.com/science/ar ... 8411003076
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