HYDRALAZINE - Blood pressure drugs - MS

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HYDRALAZINE - Blood pressure drugs - MS

Postby jackD » Wed Jan 11, 2012 8:20 pm

My doctor put me on another blood pressure drug to control my high blood pressure.

I was going to complain that I was already taking 4 other blood pressure meds and that maybe I did not need another one.

So I checked out the new one HYDRALAZINE. Results was a BIG surprise!!!

Since I am taking the HYDRALAZINE 100 mg THREE TIMES a day I feel that I might well get this "other" unexpected MS reducing benefit.

http://en.wikipedia.org/wiki/Hydralazine

extract of important part

"Pre-clinical research Multiple sclerosis: Due to its ability to damage myelin nerve sheaths, acrolein may be a factor in the development of multiple sclerosis. Hydralazine, a known scavenger of acrolein, was found to reduce myelin damage and significantly improve behavioral outcomes in a mouse model of multiple sclerosis (experimental autoimmune encephalomyelitis).[6]"
Neuroscience. 2011 Jan 26;173:150-5. Epub 2010 Nov 26.

Anti-acrolein treatment improves behavioral outcome and alleviates myelin damage in experimental autoimmune encephalomyelitis mouse.

Leung G, Sun W, Zheng L, Brookes S, Tully M, Shi R.

SourceDepartment of Basic Medical Sciences, Center for Paralysis Research, Purdue University, West Lafayette, IN 47907, USA.

Abstract
Oxidative stress is considered a major contributor in the pathology of multiple sclerosis (MS). Acrolein, a highly reactive aldehyde byproduct of lipid peroxidation, is thought to perpetuate oxidative stress. In this study, we aimed to determine the role of acrolein in an animal model of MS, experimental autoimmune encephalomyelitis (EAE) mice. We have demonstrated a significant elevation of acrolein protein adduct levels in EAE mouse spinal cord. Hydralazine, a known acrolein scavenger, significantly improved behavioral outcomes and lessened myelin damage in spinal cord. We postulate that acrolein is an important pathological factor and likely a novel therapeutic target in MS.

© 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

PMID:21081153[PubMed - indexed for MEDLINE] PMCID: PMC3034379[Available on 2012/1/26]



Mol Nutr Food Res. 2011 Sep;55(9):1320-31. doi: 10.1002/mnfr.201100217. Epub 2011 Aug 8.

Acrolein-mediated injury in nervous system trauma and diseases.

Shi R, Rickett T, Sun W.

SourceDepartment of Basic Medical Sciences, Purdue University, West Lafayette, IN 47907-1244, USA.

Abstract
Acrolein, an α,β-unsaturated aldehyde, is a ubiquitous pollutant that is also produced endogenously through lipid peroxidation. This compound is hundreds of times more reactive than other aldehydes such as 4-hydroxynonenal, is produced at much higher concentrations, and persists in solution for much longer than better known free radicals. It has been implicated in disease states known to involve chronic oxidative stress, particularly spinal cord injury and multiple sclerosis.

Acrolein may overwhelm the anti-oxidative systems of any cell by depleting glutathione reserves, preventing glutathione regeneration, and inactivating protective enzymes.

On the cellular level, acrolein exposure can cause membrane damage, mitochondrial dysfunction, and myelin disruption. Such pathologies can be exacerbated by increased concentrations or duration of exposure, and can occur in normal tissue incubated with injured spinal cord, showing that acrolein can act as a diffusive agent, spreading secondary injury.

Several chemical species are capable of binding and inactivating acrolein. Hydralazine in particular can reduce acrolein concentrations and inhibit acrolein-mediated pathologies in vivo. Acrolein scavenging appears to be a novel effective treatment, which is primed for rapid translation to the clinic.

Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PMID:21823221[PubMed - in process]
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Re: HYDRALAZINE - Blood pressure drug - MS

Postby NHE » Thu Jan 12, 2012 2:10 am

Here's an interesting paper discussing the sources of acrolein and the chemistry of its generation. It also provides some ideas for minimizing one's exposure.

http://www.ncbi.nlm.nih.gov/pmc/article ... ool=pubmed

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Re: HYDRALAZINE - Blood pressure drug - MS

Postby CureOrBust » Thu Jan 12, 2012 2:35 am

I for one would be appreciative to hear how you go, and good luck.
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Re: HYDRALAZINE - Blood pressure drug - MS

Postby jackD » Mon Jan 30, 2012 6:24 am

I am taking hydralazine 100 mg three times day for high blood pressure. It is a shame it is not approved for MS.

jackD

"Hypertension drug may delay onset, reduce severity of MS symptoms
People suffering from multiple sclerosis may benefit if patent-pending research conducted at Purdue University shows that a decades-old drug approved by the FDA to treat hypertension also delays the onset and reduces the severity of MS symptoms.

Purdue professor Riyi Shi is examining the effects of hydralazine on acrolein, a compound that can affect the central nervous system and damage nerve cells. Acrolein reacts with proteins and lipids that make up cells, including neurons. Hydralazine sequesters acrolein and acrolein-protein compounds, leading to their expulsion from the body.

Shi's research focuses on discovering the effective dosage levels to combat acrolein.

"Hydralazine usage in paediatric patients is 7.5 mg per kg of body weight, but we began testing at a much lower ratio: 1 mg per kg of body weight, which has turned out to be effective in delaying the onset of symptoms and lowering their severity in an animal model of MS," he said. "We have discovered that this dosage level does not cause a significant blood pressure drop or other side effects associated with using higher dosage levels for extended periods of time. We expect that potential use in human MS patients would be at significantly lower doses than the treatment for hypertension."

Hydralazine therapy for MS is not ready for clinical usage said Shi, a medical doctor and a professor of neuroscience and biomedical engineering in Purdue's Department of Basic Medical Sciences, School of Veterinary Medicine, Center for Paralysis Research and Weldon School of Biomedical Engineering.

Shi's first study, published in the journal Neuroscience, tested hydralazine's effectiveness before MS symptoms developed. He will follow up with studies to identify optimal treatment timing and dosage.

"We currently are testing to see if hydralazine can reduce symptoms if treatment starts after they begin," he said. "If the drug continues to prove effective, we have good reason to think it might be useful in human MS patients."

Source: Medical News Today © 2011 MediLexicon International Ltd (16/03/11)
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Re: HYDRALAZINE - Blood pressure drug - MS

Postby jackD » Sat Feb 18, 2012 11:30 am

I also had my doctor change my ACE inhbitor drug to CAPTOPRIL because the below abstract indicates it COULD help MS folks.

Yes!!! I have high blood pressure.!!!!!!

jackD

p.s. THE RATS LOVED THE STUFF TOO!

Immunopharmacol Immunotoxicol. 1995 Aug;17(3):471-91.

Effects of the angiotensin converting enzyme inhibitor captopril on experimental autoimmune encephalomyelitis.

Constantinescu CS, Ventura E, Hilliard B, Rostami A.
SourceDepartment of Neurology, University of Pennsylvania, Philadelphia 19104, USA.

Abstract
Angiotensin converting enzyme (ACE)1 mediates inflammation, participates in T cell stimulation by certain antigenic peptides, and influences the permeability of the blood brain barrier (BBB).

ACE is elevated in multiple sclerosis (MS), an autoimmune disease of the central nervous system (CNS), characterized by increased BBB permeability.

ACE inhibitor captopril suppresses certain immune functions and inhibits inflammatory or autoimmune diseases.

We studied the effect of captopril on Lewis rat EAE, an animal model of MS. Fourteen rats with EAE were treated with captopril 30 mg/kg daily from immunization to day 21 post-immunization, and compared with 14 untreated rats. Severity scores and lymphocyte reactivity to myelin basic protein and mitogen were measured. There was a statistically significant (p < 0.05) difference between the mean and cumulative clinical scores of captopril-treated and untreated animals.

Lymphocytes from captopril treated EAE rats at the peak of disease severity had diminished responses to MBP and concanavalin A. The data suggest a significant beneficial effect of captopril in Lewis rat EAE.

Further studies including other inhibitors of ACE or of other peptidases with immune, inflammatory or BBB role, may identify potentially valuable immunopharmacologic agents.

PMID:8576541[PubMed - indexed for MEDLINE]
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Re: HYDRALAZINE - Blood pressure drug - MS

Postby LR1234 » Wed Feb 22, 2012 9:16 am

Are you any better Jack (in terms of MS symptoms?)
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Re: HYDRALAZINE - Blood pressure drug - MS

Postby jackD » Wed Feb 22, 2012 10:20 pm

LR1234 wrote:Are you any better Jack (in terms of MS symptoms?)


Yes! Thank You!

I have posted that in addition to these BP drugs that help I have an extensive amount of supplements that I take. (mostly flavinoids)

Tonight I went to get get some meds at the drug store and I forgot to use my cane for the first time in 4 year! I felt akward but I made it back to my car in the parking lot.

I have been walking around my house a little without the cane for the last 4 weeks.

I took Avonex for 10 years and my MRI results were so good (no new or enhancing lesions in 6 years) I decided to just STOP the Avonex..

jackD
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Re: HYDRALAZINE - Blood pressure drugs - MS

Postby tzootsi » Fri Feb 24, 2012 7:25 am

Interesting... another blood pressure med, Lisinopril, is also being looked at as a possible ms treatment.

http://www.webmd.com/multiple-sclerosis/news/20090817/blood-pressure-drug-may-help-treat-ms
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Re: HYDRALAZINE - Blood pressure drugs - MS

Postby jackD » Fri Feb 24, 2012 3:07 pm

tzootsi wrote:Interesting... another blood pressure med, Lisinopril, is also being looked at as a possible ms treatment.

http://www.webmd.com/multiple-sclerosis/news/20090817/blood-pressure-drug-may-help-treat-ms


I have been following almost ALL the published research of "Larry" - Lawrence Steinman, MD, of Stanford University since Sep 93.

I bought a SCIENTIFIC AMERICIAN Specl edition Sep 93 on The Immune System at my local supermarket two years before I was Dxd with MS.

I found an article in it by him on "HOW MS PROGRESSES". The tech terms are a little different but he maps it out quite well.

He even indicated 5 points in which meds could be made to STOP the progression.

http://home.ix.netcom.com/~jdalton/autoimmunity.pdf

I think he later went on to help develope two of them.

His later article on the two stages of MS is fantastic.

http://home.ix.netcom.com/~jdalton/ms-two-stages.pdf

It appears "Larry" has high blood pressure so when his doctor put him on the ACE Inhibitor Lisinopril he did a search on it to get the med facts on it.

He had his computer add "Multiple Sclerosis" to all his searches automatically so was quite surprised when he found that it had positive effect on slowing MS activity.

As I posted above, I am taking the ACE drug Captopril which seems to have the same effect. I must take it three times a day. The Lisinopril is a one pill a day ACE drug.

The three times a day is a bit of a pain but I am going to stick with it because my research reveals OTHER BIG advantages for ME with the Captopril.

I have real BIG chance of having Prostate Cancer. My biopsy found ASAP cells which means I have a 40% chance of having it now or a 60% chance of getting it in the near futue.

Captopril is the ONLY ACE drug that seems to be VERY anti-cancer.

jackD

Prostate. 2004 Jan 1;58(1):50-6.

Association between captopril, other antihypertensive drugs and risk of prostate cancer.

Ronquist G, Rodríguez LA, Ruigómez A, Johansson S, Wallander MA, Frithz G, Svärdsudd K.

SourceDepartment of Medical Sciences, Clinical Chemistry, University Hospital, Uppsala, Sweden.

Abstract
BACKGROUND: There has been some debate on the existence of an association between hypertension, antihypertensive medications and cancer risk.

METHODS: We performed a nested case-control study to assess the association between the risk of prostate cancer and the use of the angiotensin converting enzyme (ACE)-inhibitor captopril, and other antihypertensive drugs. We used data from the General Practice Research Database in UK.

RESULTS: We found an incidence rate of prostate cancer of 1.61 per 1,000 person-years among male patients aged 50-79 years old.

Patients with a history of benign prostatic hyperplasia and/or prostatism carried a two-fold greater risk of prostate cancer than those without such antecedents.

None of the other studied co-morbidities were associated with prostate cancer.

We found that users of captopril had a relative risk of 0.7 (95% CI: 0.4-1.2) to develope prostate cancer.

None of the other studied individual ACE-inhibitors shared a similar effect with the one observed for captopril
.

CONCLUSIONS: No clear association was apparent between the use of antihypertensive drugs and prostate cancer. However, specific focus on users of captopril showed a lower risk of subsequent prostate cancer. Further research is needed to explore this association.

Copyright 2003 Wiley-Liss, Inc.

PMID:14673952[PubMed - indexed for MEDLINE]


Scand J Urol Nephrol. 2009;43(1):32-6.

Captopril may reduce biochemical (prostate-specific antigen) failure following radical prostatectomy for clinically localized prostate cancer.

Ronquist G, Frithz G, Wang YH, Lindeborg T.
SourceDepartment of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden.

Abstract
OBJECTIVE: A prior report suggested that individuals medicated with captopril showed a decreased incidence of prostate cancer. This study therefore investigated whether captopril given postoperatively had any preventive effect on biochemical recurrence for patients treated with radical prostatectomy.

MATERIAL AND METHODS: Data were prospectively reviewed for 62 men subjected to radical retropubic prostatectomy due to biopsy-confirmed, clinically localized prostate cancer and comparisons were made between two groups, those receiving captopril postoperatively (12.5 mg twice daily; captopril group, n=32) and those not receiving any captopril (control group, n=30). One surgeon carried out the surgery.

RESULTS: The two groups were comparable as regards age at surgery, prostate volume, preoperative prostate-specific antigen values, pathological stage, Gleason score, organ-confined disease, occurrence of positive surgical margins and extraprostatic extension. The incidence of biochemical failure was three out of 32 patients in the captopril group and 10 out of 30 in the control group (p=0.034) during a mean observational time of 29 months.

CONCLUSIONS: A lower rate of biochemical recurrence was observed in men subjected to radical prostatectomy treated with captopril postoperatively than in those not receiving captopril. These results were based on only 32 observations; a larger study may show no evidence of an association.

PMID:18932051[PubMed - indexed for MEDLINE]


THIS ANTI-CANCER EFFECT OF CAPTOPRIL SEEMS TO EXTEND TO OTHER CANCERS.

Ann N Y Acad Sci. 2008 Sep;1138:65-72.

Captopril as a potential inhibitor of lung tumor growth and metastasis.

Attoub S, Gaben AM, Al-Salam S, Al Sultan MA, John A, Nicholls MG, Mester J, Petroianu G.

SourceDepartment of Pharmacology, Faculty of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.

Abstract
Lung cancer is the most common form of cancer in the world, and 90% of patients die from their disease.

The angiotensin converting enzyme (ACE) inhibitors are used widely as antihypertensive agents, and it has been suggested that they decrease the risk of some cancers, although available data are conflicting. Accordingly, we investigated the anticancer activity of the ACE inhibitor, captopril, in athymic mice injected with highly tumorigenic LNM35 human lung cells as xenografts.

Using this model, we demonstrated that daily IP administration of captopril (2.8 mg/mouse) for 3 weeks resulted in a remarkable reduction of tumor growth (58%, P < 0.01) and lymph node metastasis (50%, P= 0.088).

There were no undesirable effects of captopril treatment on animal behavior and body weight. In order to determine the mechanism by which captopril inhibited tumor growth, we investigated the impact of this drug on cell proliferation, apoptosis, and angiogenesis. Immunohistochemical analysis demonstrated that captopril treatment significantly reduced the number of proliferating cells (Ki-67) in the tumor samples but was not associated with inhibition of tumor angiogenesis (CD31). Using cell viability and fluorescent activated cell sorting analysis tests, we demonstrated that captopril inhibited the viability of LNM35 cells by inducing apoptosis, providing insight about the mechanisms underlying its antitumorigenic activities.

In view of these experimental findings, we conclude that captopril could be a promising option for the treatment of lung cancer.

PMID:18837885[PubMed - indexed for MEDLINE]
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Re: HYDRALAZINE - Blood pressure drugs - MS

Postby jackD » Fri Feb 24, 2012 3:50 pm

Just for the record I want to add I have a third BP drug I take that has a POTENT anti-cancer effect.

The GENERIC name is (telmisartan) but it is only available as BRAND NAME -"MICARDIS".

http://home.ix.netcom.com/~jdalton/Telmisartan.pdf

jackD

Oncol Rep. 2008 Aug;20(2):295-300.

Telmisartan is a potent target for prevention and treatment in human prostate cancer.

Funao K, Matsuyama M, Kawahito Y, Sano H, Chargui J, Touraine JL, Nakatani T, Yoshimura R.
SourceDepartment of Urology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan.

Abstract
Angiotensin II receptor blockers (ARBs) are widely used as hypertensive therapeutic agent. Recent studies have reported that ARBs have the potential to inhibit the growth of prostate cancer (PC) cells. Moreover, it was recently reported that Telmisartan (a kind of ARB) has peroxisome proliferator-activated receptor (PPAR)-gamma activation. We previously reported that PPAR-gamma ligand induces growth arrest of PC cells through apoptosis. In this study, we evaluated the effects of the Telmisartan and other ARBs on cell proliferation in several PC cell lines. We used normal prostate stromal cell (NPC), human hormone-refractory PC (PC3), androgen-independent PC (DU-145) and androgen-dependent PC (LNCaP) cell lines. Effects of Telmisartan and other ARBs (Candesartan, Valsartan, Irbesartan and Losartan) on PC cell growth were examined by MTT assay. Flow cytometry and Hoechst staining were used to determine whether or not ARBs induce apoptosis.

Telmisartan caused marked inhibition of PC cells in concentration-dependent and time-dependent manner. PC cells with treatment of 100 microM Telmisartan induced early apoptosis and DNA fragmentation. However, NPC with treatment of 100 microM Telmisartan did not induce apoptosis or DNA fragmentation.

Furthermore, other ARBs had no effect on cell proliferation in the PC cells and NPC.

Telmisartan may mediate potent antiproliferative effects against PC cells through PPAR-gamma.

Thus, Telmisartan is a potent target for prevention and treatment in PC.

PMID:18636189[PubMed - indexed for MEDLINE]
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Re: HYDRALAZINE - Blood pressure drugs - MS

Postby Taurus » Sat Mar 31, 2012 12:52 am

Hi Folks, any body taking Lisinopril or Hydrazaline for MS and has good results. Please share
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Re: HYDRALAZINE - Blood pressure drugs - MS

Postby jackD » Tue Apr 10, 2012 11:52 am

Here is WHY Acrolein is so bad forMS folks...

"Due to its ability to damage myelin nerve sheaths, acrolein may be a factor in the development of multiple sclerosis. The antihypertensive drug hydralazine, a known scavenger of acrolein, was found to reduce myelin damage and significantly improve behavioral outcomes in a mouse model of multiple sclerosis (experimental autoimmune encephalomyelitis).[6]"


http://en.wikipedia.org/wiki/Acrolein



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Re: HYDRALAZINE - Blood pressure drugs - MS

Postby jackD » Wed Apr 11, 2012 7:46 pm

Some comments on Acrolein .

This stuff is formed when common cooking oils used in frying pans starts to smoke.

One simple solution is to use "Peanut Oil" which is a "high temperature" cooking oil that resists smoking at normal cooking temperatures.

I expect that cooking a "ribeye" steak in a frypan or grill will also produce lots of Acroleins.
(Acrolein (CH2=CH–CHO) has the peculiar odor of burnt grease.)

Also these GREEN NUTS that burn cooking oils in their diesel cars/trucks produce tons of these Acroleins in their exaust fumes.

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Re: HYDRALAZINE - Blood pressure drugs - MS

Postby stazmatic » Tue Jul 31, 2012 1:48 pm

I know someone that just started using the BP drug Cozaar (25mg) to help treat her MS. Anyone hear of using that particular drug for MS?
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Re: HYDRALAZINE - Blood pressure drugs - MS

Postby jackD » Tue Jul 31, 2012 3:50 pm

stazmatic wrote:I know someone that just started using the BP drug Cozaar (25mg) to help treat her MS. Anyone hear of using that particular drug for MS?


The below abstract may shed some light on why and how Cozaar and similiar drugs may help MS folks.

(Losartan is an angiotensin II receptor antagonist drug used mainly to treat high blood pressure (hypertension). Losartan was the first angiotensin II receptor antagonist to be marketed. Losartan potassium is marketed by Merck & Co. Inc. under the trade name Cozaar. As of 2009, losartan is available in generic form.)

jackD


Natl Acad Sci U S A. 2009 Sep 1;106(35):14942-7. Epub 2009 Aug 19.

Role of the renin-angiotensin system in autoimmune inflammation of the central nervous system.

Stegbauer J, Lee DH, Seubert S, Ellrichmann G, Manzel A, Kvakan H, Muller DN, Gaupp S, Rump LC, Gold R, Linker RA.

Department of Nephrology, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany.

Angiotensin II is the principle effector molecule of the renin angiotensin system (RAS). It exerts its various actions on the cardiovascular and renal system, mainly via interaction with the angiotensin II type-1 receptor (AT1R), which contributes to blood pressure regulation and development of hypertension but may also mediate effects on the immune system.

Here we study the role of the RAS in myelin-oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (MOG-EAE), a model mimicking many aspects of multiple sclerosis.

Quantitative RT-PCR analyses showed an up-regulation of renin, angiotensin-converting enzyme, as well as AT1R in the inflamed spinal cord and the immune system, including antigen presenting cells (APC). Treatment with the renin inhibitor aliskiren, the angiotensin II converting-enzyme inhibitor enalapril, as well as preventive or therapeutic application of the AT1R antagonist losartan, resulted in a significantly ameliorated course of MOG-EAE. Blockade of AT1R did not directly impact on T-cell responses, but significantly reduced numbers of CD11b+ or CD11c+ APC in immune organs and in the inflamed spinal cord. Additionally, AT1R blockade impaired the expression of CCL2, CCL3, and CXCL10, and reduced CCL2-induced APC migration.

Our findings suggest a pivotal role of the RAS in autoimmune inflammation of the central nervous system and identify RAS blockade as a potential new target for multiple sclerosis therapy.

PMID: 19706425 [PubMed - indexed for MEDLINE] PMCID: PMC2736426
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