Re: Angiotensin Receptor Blockers and Glutathione

[Guest guest]

IMO, the benefits of ARBs and modalities that raise glutathione are

not only compatible, but are likely additive.

> Hi, all.

>

> In the past there has been discussion on some of the lists about

> whether making efforts to build glutathione would be compatible

with

> taking an angiotensin receptor blocker (ARB).

>

> I found four papers in the literature that report investigations

> into the effect of ARBs on the glutathione status in rats and in

> humans. The abstracts of these papers are pasted below.

>

> All four papers report that it was found that ARBs raised

> glutathione and decreased the state of oxidative stress.

>

> I think that this suggests that glutathione building is compatible

> with taking ARBs.

>

> In addition, it may also suggest that one of the ways in which ARBs

> are beneficial to some people might be their effect on raising

> glutathione and lowering oxidative stress.

>

> Please note that I am neither advocating the use of ARBs or

opposing

> them, only trying to understand the interactions.

>

> Rich

>

>

> Jpn J Physiol. 2002 Oct;52(5):435-40.

>

> The effects of losartan and enalapril therapies on the levels of

> nitric oxide, malondialdehyde, and glutathione in patients with

> essential hypertension.

>

> Donmez G, Derici U, Erbas D, Arinsoy T, Onk A, Sindel S, Hasanoglu

E.

>

> Department of Physiology, Gazi University Faculty of Medicine,

> Ankara, 06510 Turkey.

>

> Several recent studies have shown that essential hypertension is

> associated with increased oxidative stress, which may cause

> hypertension via enhanced oxidation and inactivation of nitric

> oxide. In this study, we investigated the malondialdehyde, nitric

> oxide, and glutathione levels in newly diagnosed essential

> hypertensive patients and whether or not there was any effect of

> antihypertensive treatment with angiotensin II type 1 receptor

> antagonist, losartan or angiotensin converting enzyme inhibitor,

> enalapril on plasma malondialdehyde, nitric oxide, and glutathione

> values. We selected 17 patients (F/M: 10/7, mean age: 46.12 +/- 9.2

> years) for enalapril therapy (10-20 mg/d) and 14 patients (F/M:

8/6,

> mean age: 47.7 +/- 7.5 years) for losartan therapy (50-100 mg/d),

> and compared them with 12 normotensive controls. At the beginning

of

> the study, both treated groups showed significantly higher plasma

> malondialdehyde and lower glutathione and nitric oxide in exhaled

> air compared to the control group. After 9 weeks of enalapril and

> losartan treatment, both systolic and diastolic pressure were

> significantly reduced. Both enalapril and losartan produced a

> significant decrease in plasma malondialdehyde and a significant

> increase in plasma glutathione levels and nitric oxide in exhaled

> air after 9 weeks. Initial values of plasma nitrate levels in

> patient groups were similar to the control group and increased

> significantly after the treatment period. In conclusion, both

> losartan and enalapril may be regulators between oxidant stress and

> the antioxidant system.

>

> PMID: 12533248 [PubMed - indexed for MEDLINE]

>

>

> FASEB J. 2003 Jun;17(9):1096-8. Epub 2003 Apr 22.

>

> Enalapril and losartan attenuate mitochondrial dysfunction in aged

> rats.

>

> de Cavanagh EM, Piotrkowski B, Basso N, Stella I, Inserra F, Ferder

> L, Fraga CG.

>

> Physical Chemistry-PRALIB, School of Pharmacy and Biochemistry,

> University of Buenos Aires, Argentina.

>

> Renin-angiotensin system (RAS) inhibition can attenuate the effects

> of aging on renal function and structure; however, its effect on

> mitochondrial aging is unknown. To investigate whether an

> angiotensin-converting enzyme inhibitor (enalapril) or an

> angiotensin II receptor blocker (losartan) could mitigate age-

> associated changes in kidney mitochondria, male Wistar rats (14 mo

> old) received during 8 mo water containing either enalapril (10

> mg/kg/day) (Enal), or losartan (30 mg/kg/day) (Los), or no

additions

> (Old). Four-month-old untreated rats (Young) were also studied. In

> old rats mitochondrial respiratory control, ADP/O, nitric oxide

> synthase activity, and uncoupling protein 2 levels were lower (46,

> 42, 27, and 76%, respectively), and Mn-SOD activity was higher

(70%)

> than in Young, Enal, and Los rats. In Old rats mitochondrial

> hydrogen peroxide production was higher than in both Young (197%)

> and Enal or Los (40%) rats. In Old rats, kidney GSH/GSSG was lower

> than in both Young (80%) and Enal (57%) or Los (68%) rats. In Old

> rats electron microscopy showed effacement of microvilli in tubular

> epithelial cells, ill-defined mitochondrial cristae, lower

> mitochondrial numbers, and enhanced number of osmiophilic bodies

> relative to Young, Enal, or Los rats. In conclusion, enalapril and

> losartan can protect against both age-related mitochondrial

> dysfunction and ultrastructural alterations, underscoring the role

> of RAS in the aging process. An association with oxidative stress

> modulation is suggested.

>

> PMID: 12709417 [PubMed - indexed for MEDLINE]

>

> -------------------------------------------------------------------

--

> -----------

>

> Mol Aspects Med. 2004 Feb-Apr;25(1-2):27-36.

>

> Concerted action of the renin-angiotensin system, mitochondria, and

> antioxidant defenses in aging.

>

> de Cavanagh EM, Piotrkowski B, Fraga CG.

>

> Physical Chemistry-PRALIB, School of Pharmacy and Biochemistry,

> University of Buenos Aires, Junin 956, 1113 Buenos Aires,

Argentina.

>

> Angiotensin-converting enzyme inhibitors (ACEi) and AT-1 receptor

> blockers (ARB) are two types of drugs that inhibit the renin-

> angiotensin system (RAS), and can attenuate the progression to

> cardiac and/or renal functional impairment, secondary to diverse

> pathologies. Some of the beneficial effects of ACEi and ARB occur

> independently of the ability of these drugs to reduce arterial

blood

> pressure. Both, in animals, and in humans, we observed an

> enhancement of antioxidant defenses that occurred after treatment

> with ACEi. Based on these results, we postulate that some of the

> beneficial health effects associated to RAS inhibition can be

> ascribed to the prevention of oxidant-mediated damage. Furthermore,

> considering that: (i). RAS inhibition attenuates certain age-

> associated degenerative changes; (ii). aging was postulated to

> result from the accumulation of oxidant-mediated damage; and (iii).

> mitochondria are a major source of oxidants, we studied potential

> associations among RAS inhibition, mitochondrial function and

> production of oxidants and nitric oxide, and aging. The results

> obtained suggest, that RAS inhibitors, i.e. enalapril and losartan,

> can protect against the effects of aging by attenuating oxidant

> damage to mitochondria, and in consequence, they preserve

> mitochondrial function. The mechanism(s) explaining such

attenuation

> of oxidant damage can relay on a reduction of the ANG-II-dependent

> generation of superoxide and/or an increased detoxification of

> reactive nitrogen and oxygen species by recomposition of

antioxidant

> defense levels.

>

> PMID: 15051314 [PubMed - indexed for MEDLINE]

>

>

> Am J Hypertens. 2004 Sep;17(9):809-16.

>

> Factors related to the impact of antihypertensive treatment in

> antioxidant activities and oxidative stress by-products in human

> hypertension.

>

> Saez GT, Tormos C, Giner V, Chaves J, Lozano JV, Iradi A, Redon J.

>

> Department of Biochemistry and Molecular Biology, Medical School,

> Valencia, Spain.

>

> The objective was to study factors related to the changes induced

by

> antihypertensive treatment on oxidative status, antioxidant

> activities, and reactive oxygen species by-products in whole blood

> and mononuclear peripheral cells. Eighty-nine hypertensive patients

> (mean age 46 years, 46 men, average 24-h blood pressure 139/88 mm

> Hg, body mass index 29) were included. After 3 months of

> nonrandomized allocation to antihypertensive treatment (20

> nonpharmacologic, 36 beta-blockers, 33 angiotensin receptor

> blocker), oxidized/reduced glutathione ratio and malondialdehyde

> were significantly reduced, and the activity of superoxide

> dismutase, catalase, and glutathione peroxidase was significantly

> increased in both whole blood and peripheral mononuclear cells. The

> content of damaged base 8-oxo-2'-deoxyguanosine in nuclear and

> mitochondrial DNA in hypertensive subjects was also significantly

> reduced during the antihypertensive treatment. In a group of 42

> subjects, the oxidative stress was further reduced and the

> antioxidant enzyme activities further increased after 12 months of

> antihypertensive treatment. The changes were independent of the

kind

> of antihypertensive treatment. In conclusion, antihypertensive

> treatment improved the increased oxidative stress and the decreased

> antioxidant mechanisms. It is independent of the type of treatment

> and the beneficial effect of treatment increases over time.

> Copyright 2004 American Journal of Hypertension, Ltd.

>

> PMID: 15363824 [PubMed - indexed for MEDLINE]

[Guest guest]

I don't prefer ACE inhibitors because kinins are degraded by ACE and

we don't want to inhibit the degradation of kinins in inflammatory

disease.

ARBs are a better choice, IMO. Benicar (olmesartan) or Micardis

(telmisartan) would be preferred over Cozaar (losartan) since they

are not metabolized via the P450 pathway as is losartan.

Low-doses work well for reducing inflammation in my experience.

> > > Hi, all.

> > >

> > > In the past there has been discussion on some of the lists

about

> > > whether making efforts to build glutathione would be

compatible

> > with

> > > taking an angiotensin receptor blocker (ARB).

> > >

> > > I found four papers in the literature that report

investigations

> > > into the effect of ARBs on the glutathione status in rats and

in

> > > humans. The abstracts of these papers are pasted below.

> > >

> > > All four papers report that it was found that ARBs raised

> > > glutathione and decreased the state of oxidative stress.

> > >

> > > I think that this suggests that glutathione building is

compatible

> > > with taking ARBs.

> > >

> > > In addition, it may also suggest that one of the ways in which

ARBs

> > > are beneficial to some people might be their effect on raising

> > > glutathione and lowering oxidative stress.

> > >

> > > Please note that I am neither advocating the use of ARBs or

> > opposing

> > > them, only trying to understand the interactions.

> > >

> > > Rich

> > >

> > >

> > > Jpn J Physiol. 2002 Oct;52(5):435-40.

> > >

> > > The effects of losartan and enalapril therapies on the levels

of

> > > nitric oxide, malondialdehyde, and glutathione in patients with

> > > essential hypertension.

> > >

> > > Donmez G, Derici U, Erbas D, Arinsoy T, Onk A, Sindel S,

Hasanoglu

> > E.

> > >

> > > Department of Physiology, Gazi University Faculty of Medicine,

> > > Ankara, 06510 Turkey.

> > >

> > > Several recent studies have shown that essential hypertension

is

> > > associated with increased oxidative stress, which may cause

> > > hypertension via enhanced oxidation and inactivation of nitric

> > > oxide. In this study, we investigated the malondialdehyde,

nitric

> > > oxide, and glutathione levels in newly diagnosed essential

> > > hypertensive patients and whether or not there was any effect

of

> > > antihypertensive treatment with angiotensin II type 1 receptor

> > > antagonist, losartan or angiotensin converting enzyme

inhibitor,

> > > enalapril on plasma malondialdehyde, nitric oxide, and

glutathione

> > > values. We selected 17 patients (F/M: 10/7, mean age: 46.12 +/-

9.2

> > > years) for enalapril therapy (10-20 mg/d) and 14 patients

(F/M:

> > 8/6,

> > > mean age: 47.7 +/- 7.5 years) for losartan therapy (50-100

mg/d),

> > > and compared them with 12 normotensive controls. At the

beginning

> > of

> > > the study, both treated groups showed significantly higher

plasma

> > > malondialdehyde and lower glutathione and nitric oxide in

exhaled

> > > air compared to the control group. After 9 weeks of enalapril

and

> > > losartan treatment, both systolic and diastolic pressure were

> > > significantly reduced. Both enalapril and losartan produced a

> > > significant decrease in plasma malondialdehyde and a

significant

> > > increase in plasma glutathione levels and nitric oxide in

exhaled

> > > air after 9 weeks. Initial values of plasma nitrate levels in

> > > patient groups were similar to the control group and increased

> > > significantly after the treatment period. In conclusion, both

> > > losartan and enalapril may be regulators between oxidant

stress and

> > > the antioxidant system.

> > >

> > > PMID: 12533248 [PubMed - indexed for MEDLINE]

> > >

> > >

> > > FASEB J. 2003 Jun;17(9):1096-8. Epub 2003 Apr 22.

> > >

> > > Enalapril and losartan attenuate mitochondrial dysfunction in

aged

> > > rats.

> > >

> > > de Cavanagh EM, Piotrkowski B, Basso N, Stella I, Inserra F,

Ferder

> > > L, Fraga CG.

> > >

> > > Physical Chemistry-PRALIB, School of Pharmacy and Biochemistry,

> > > University of Buenos Aires, Argentina.

> > >

> > > Renin-angiotensin system (RAS) inhibition can attenuate the

effects

> > > of aging on renal function and structure; however, its effect

on

> > > mitochondrial aging is unknown. To investigate whether an

> > > angiotensin-converting enzyme inhibitor (enalapril) or an

> > > angiotensin II receptor blocker (losartan) could mitigate age-

> > > associated changes in kidney mitochondria, male Wistar rats

(14 mo

> > > old) received during 8 mo water containing either enalapril (10

> > > mg/kg/day) (Enal), or losartan (30 mg/kg/day) (Los), or no

> > additions

> > > (Old). Four-month-old untreated rats (Young) were also

studied. In

> > > old rats mitochondrial respiratory control, ADP/O, nitric oxide

> > > synthase activity, and uncoupling protein 2 levels were lower

(46,

> > > 42, 27, and 76%, respectively), and Mn-SOD activity was higher

> > (70%)

> > > than in Young, Enal, and Los rats. In Old rats mitochondrial

> > > hydrogen peroxide production was higher than in both Young

(197%)

> > > and Enal or Los (40%) rats. In Old rats, kidney GSH/GSSG was

lower

> > > than in both Young (80%) and Enal (57%) or Los (68%) rats. In

Old

> > > rats electron microscopy showed effacement of microvilli in

tubular

> > > epithelial cells, ill-defined mitochondrial cristae, lower

> > > mitochondrial numbers, and enhanced number of osmiophilic

bodies

> > > relative to Young, Enal, or Los rats. In conclusion, enalapril

and

> > > losartan can protect against both age-related mitochondrial

> > > dysfunction and ultrastructural alterations, underscoring the

role

> > > of RAS in the aging process. An association with oxidative

stress

> > > modulation is suggested.

> > >

> > > PMID: 12709417 [PubMed - indexed for MEDLINE]

> > >

> > > ---------------------------------------------------------------

----

> > --

> > > -----------

> > >

> > > Mol Aspects Med. 2004 Feb-Apr;25(1-2):27-36.

> > >

> > > Concerted action of the renin-angiotensin system,

mitochondria, and

> > > antioxidant defenses in aging.

> > >

> > > de Cavanagh EM, Piotrkowski B, Fraga CG.

> > >

> > > Physical Chemistry-PRALIB, School of Pharmacy and Biochemistry,

> > > University of Buenos Aires, Junin 956, 1113 Buenos Aires,

> > Argentina.

> > >

> > > Angiotensin-converting enzyme inhibitors (ACEi) and AT-1

receptor

> > > blockers (ARB) are two types of drugs that inhibit the renin-

> > > angiotensin system (RAS), and can attenuate the progression to

> > > cardiac and/or renal functional impairment, secondary to

diverse

> > > pathologies. Some of the beneficial effects of ACEi and ARB

occur

> > > independently of the ability of these drugs to reduce arterial

> > blood

> > > pressure. Both, in animals, and in humans, we observed an

> > > enhancement of antioxidant defenses that occurred after

treatment

> > > with ACEi. Based on these results, we postulate that some of

the

> > > beneficial health effects associated to RAS inhibition can be

> > > ascribed to the prevention of oxidant-mediated damage.

Furthermore,

> > > considering that: (i). RAS inhibition attenuates certain age-

> > > associated degenerative changes; (ii). aging was postulated to

> > > result from the accumulation of oxidant-mediated damage; and

(iii).

> > > mitochondria are a major source of oxidants, we studied

potential

> > > associations among RAS inhibition, mitochondrial function and

> > > production of oxidants and nitric oxide, and aging. The results

> > > obtained suggest, that RAS inhibitors, i.e. enalapril and

losartan,

> > > can protect against the effects of aging by attenuating oxidant

> > > damage to mitochondria, and in consequence, they preserve

> > > mitochondrial function. The mechanism(s) explaining such

> > attenuation

> > > of oxidant damage can relay on a reduction of the ANG-II-

dependent

> > > generation of superoxide and/or an increased detoxification of

> > > reactive nitrogen and oxygen species by recomposition of

> > antioxidant

> > > defense levels.

> > >

> > > PMID: 15051314 [PubMed - indexed for MEDLINE]

> > >

> > >

> > > Am J Hypertens. 2004 Sep;17(9):809-16.

> > >

> > > Factors related to the impact of antihypertensive treatment in

> > > antioxidant activities and oxidative stress by-products in

human

> > > hypertension.

> > >

> > > Saez GT, Tormos C, Giner V, Chaves J, Lozano JV, Iradi A,

Redon J.

> > >

> > > Department of Biochemistry and Molecular Biology, Medical

School,

> > > Valencia, Spain.

> > >

> > > The objective was to study factors related to the changes

induced

> > by

> > > antihypertensive treatment on oxidative status, antioxidant

> > > activities, and reactive oxygen species by-products in whole

blood

> > > and mononuclear peripheral cells. Eighty-nine hypertensive

patients

> > > (mean age 46 years, 46 men, average 24-h blood pressure 139/88

mm

> > > Hg, body mass index 29) were included. After 3 months of

> > > nonrandomized allocation to antihypertensive treatment (20

> > > nonpharmacologic, 36 beta-blockers, 33 angiotensin receptor

> > > blocker), oxidized/reduced glutathione ratio and

malondialdehyde

> > > were significantly reduced, and the activity of superoxide

> > > dismutase, catalase, and glutathione peroxidase was

significantly

> > > increased in both whole blood and peripheral mononuclear

cells. The

> > > content of damaged base 8-oxo-2'-deoxyguanosine in nuclear and

> > > mitochondrial DNA in hypertensive subjects was also

significantly

> > > reduced during the antihypertensive treatment. In a group of 42

> > > subjects, the oxidative stress was further reduced and the

> > > antioxidant enzyme activities further increased after 12

months of

> > > antihypertensive treatment. The changes were independent of

the

> > kind

> > > of antihypertensive treatment. In conclusion, antihypertensive

> > > treatment improved the increased oxidative stress and the

decreased

> > > antioxidant mechanisms. It is independent of the type of

treatment

> > > and the beneficial effect of treatment increases over time.

> > > Copyright 2004 American Journal of Hypertension, Ltd.

> > >

> > > PMID: 15363824 [PubMed - indexed for MEDLINE]

> >

> >

> >

> >

> >

> >

> >