Angiotensin Receptor Blockers and Glutathione
as reported by Rich Van Konynenburg (richvank@AOL.COM)
(5/11/05)
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Angiotensin Receptor Blockers and Glutathione as reported by Rich Van Konynenburg (richvank@AOL.COM) (5/11/05) |
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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 found 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 (and am an engineer NOT an M.D.).
Rich Van Konynenburg, Ph.D.
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 gluta! thione 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]
From: Jpn J Physiol. 2002 Oct;52(5):435-40.
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 r! ats, 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]
From: FASEB J. 2003 Jun;17(9):1096-8. Epub 2003 Apr 22.
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 oxid! ants, 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]
From: Mol Aspects Med. 2004 Feb-Apr;25(1-2):27-36.
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]
From: Am J Hypertens. 2004 Sep;17(9):809-16.
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