The antioxidant effect of angiotensin II receptor blocker, losartan, in streptozotocin-induced diabetic rats

Kamper, Maria; Tsimpoukidi, O.; Chatzigeorgiou, Antonios; Lymberi, Maria; Kamper, Elli F.

doi:10.1016/j.trsl.2010.05.004

Cited by 36 publications

(28 citation statements)

References 52 publications

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“…On the other hand, losartan has several AT1 receptor-independent actions, including its anti-inflammatory and antioxidant properties. 20, 21 An animal study suggested that free radicals and oxidative stress may involve in angiotensin II-induced α-klotho down-regulation. 9 Hence, it is possible that increased α-klotho by losartan might also be partially attributable to its antioxidant effect.…”

Section: Discussionmentioning

confidence: 99%

Elevated circulating alpha-klotho by angiotensin II receptor blocker losartan is associated with reduction of albuminuria in type 2 diabetic patients

Lim

Liu

Tavintharan

et al. 2013

J Renin Angiotensin Aldosterone Syst

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Introduction:The aging-suppression gene α-klotho is potentially reno-protective. Animal studies suggest that angiotensin II may be a negative regulator of α-klotho expression. Therefore, we hypothesize that renin-angiotensin system antagonism may increase α-klotho secretion in type 2 diabetes (T2DM). Subjects and methods:In this post-hoc analysis of a randomized crossover study, 33 T2DM subjects with albuminuria received either 50 mg of losartan or 20 mg of quinapril (both 50% maximal dose) daily for 4 weeks with 4-week washout period in between. Results: Our data showed that losartan, but not quinapril, significantly increased circulating α-klotho level by an average of 23% (from 542 pg/ml to 668 pg/ml, p=0.001). Linear regression revealed that, besides different mode of treatment, increment in plasma α-klotho was associated with decrement in urine albumin/creatinine ratio (β=-0.263, p=0.029). Conclusions: The angiotensin receptor blocker losartan increases circulating α-klotho in T2DM with albuminuria. The clinical significance of this rise in α-klotho associated with losartan intervention deserves further investigation.

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Section: Discussionmentioning

confidence: 99%

Elevated circulating alpha-klotho by angiotensin II receptor blocker losartan is associated with reduction of albuminuria in type 2 diabetic patients

Lim

Liu

Tavintharan

et al. 2013

J Renin Angiotensin Aldosterone Syst

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“…3,[84][85][86][87][88][89] CONCLUSIONS In summary, Ang-(1-7) is generated in the vascular wall and other tissues from Ang II by ACE2, resulting in a decrease in Ang II levels and an increase in Ang-(1-7) concentrations in the vessels. Thus, the ACE2-Ang-(1-7)-Mas axis counterregulates the classic RAAS in tissues responsible for blood pressure regulation and cardiovascular homeostasis.…”

Section: Redox-sensitive Signaling By the Ace2-ang-(1-7)-mas Axismentioning

confidence: 94%

“…[85][86][87][88] Sampaio et al 89 showed that the activation of this enzymatic complex by Ang II is attenuated by Ang-(1-7) in human endothelial cells. The authors suggest that the principal mechanism involves the interaction of this peptide with Mas, leading to the activation of AKT.…”

Section: Redox-sensitive Signaling By the Ace2-ang-(1-7)-mas Axismentioning

confidence: 99%

ACE2–angiotensin-(1–7)–Mas axis and oxidative stress in cardiovascular disease

2010

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The renin-angiotensin-aldosterone system (RAAS) is a pivotal regulator of physiological homeostasis and diseases of the cardiovascular system. Recently, new factors have been discovered, such as angiotensin-converting enzyme 2 (ACE2), angiotensin-(1-7) and Mas. This newly defined ACE2-angiotensin-(1-7)-Mas axis was shown to have a critical role in the vasculature and in the heart, exerting mainly protective effects. One important mechanism of the classic and the new RAAS regulate vascular function is through the regulation of redox signaling. Angiotensin II is a classic prooxidant peptide that increases superoxide production through the activation of NAD(P)H oxidases. This review summarizes the current knowledge about the ACE2-angiotensin-(1-7)-Mas axis and redox signaling in the context of cardiovascular regulation and disease. By interacting with its receptor Mas, angiotensin-(1-7) induces the release of nitric oxide from endothelial cells and thereby counteracts the effects of angiotensin II. ACE2 converts angiotensin II to angiotensin-(1-7) and, thus, is a pivotal regulator of the local effects of the RAAS on the vessel wall. Taken together, the ACE2-angiotensin-(1-7)-Mas axis emerges as a novel therapeutic target in the context of cardiovascular and metabolic diseases.

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“…Losartan is reported to increase NO release 13 . Losartan is known to decrease the production of reactive oxygen species and supress lipid peroxidation 14 . Losartan is also reported to prevent progression of many chronic renal diseases such as diabetic nephropathy 12 .…”

Section: Introductionmentioning

confidence: 99%

Effects of Losartan on Glycerol-induced Myoglobinuric Acute Renal Failure in Rats

Kaya¹,

Aydoğdu²,

Taştekin³

et al. 2013

Kafkas Univ Vet Fak Derg

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SummaryMyoglobinuric acute renal failure (mARF) is an uremic syndrome which develops due to damage of skeletal muscle. It was demonstrated that free radicals and nitric oxide (NO) play an important role in pathogenesis of mARF. Our aim was to investigate the effect of losartan, a drug known for its antioxidant effect, on mARF. In our study, a total of 34 male Spraque Dawley rats were divided into four groups. 1 st and 2 nd groups were injected with saline, 3 rd and 4 th groups were injected with intramuscular glycerol. One and 24 hours later, 1 st and 3 rd groups received saline orally and 2 nd and 4 th groups have taken 10 mg/kg losartan. Urine was collected; the blood samples and kidneys of the rats were taken under the anesthesia. The levels of NO, arginine, asymmetric dimethylarginine (ADMA), glutathione (GSH) and malondialdehyde (MDA) were determined, renal functions and histopathological changes examined. In our study, we found that levels of urea, creatinine, and potassium, in serum samples and MDA and ADMA in renal tissue were increased in 3 rd group when it's compared with the 1 st group. Levels of sodium, arginine in serum samples and arginine in renal tissue were reduced 3 rd group when compared with the 1 st group. When 3 rd and 4 th groups were compared, serum creatinine was higher in the latter group whereas ADMA level in renal tissue was lower in the same group. We think that there is no positive effect of losartan on the pathogenesis of mARF.

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The antioxidant effect of angiotensin II receptor blocker, losartan, in streptozotocin-induced diabetic rats

Cited by 36 publications

References 52 publications

Elevated circulating alpha-klotho by angiotensin II receptor blocker losartan is associated with reduction of albuminuria in type 2 diabetic patients

Elevated circulating alpha-klotho by angiotensin II receptor blocker losartan is associated with reduction of albuminuria in type 2 diabetic patients

ACE2–angiotensin-(1–7)–Mas axis and oxidative stress in cardiovascular disease

Effects of Losartan on Glycerol-induced Myoglobinuric Acute Renal Failure in Rats

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