The direct antioxidative and anti-inflammatory effects of peroxisome proliferator-activated receptors ligands are associated with the inhibition of angiotensin converting enzyme expression in streptozotocin-induced diabetic rat aorta

Toba, Hiroe; Miki, Shunsuke; Shimizu, Takahiro; Yoshimura, Akiko; Inoue, Riyako; Sawai, Naoki; Tsukamoto, Rie; Murakami, Masahumi; Morita, Yoshifumi; Nakayama, Yusuke; Kobara, Miyuki; Nakata, Tetsuo

doi:10.1016/j.ejphar.2006.08.036

Cited by 36 publications

(32 citation statements)

References 35 publications

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“…37 Indeed, isome-proliferator activated receptors ␣ and ␥ agonists were shown recently to suppress vascular ACE expression in stretozotocin-induced diabetic rats. 38 …”

Section: Ace and Renin Mrna Expression In Renal And Adipose Tissues Omentioning

confidence: 99%

Developmental Programming of Renal Glucocorticoid Sensitivity and the Renin-Angiotensin System

2007

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Abstract-Fetal glucocorticoid excess leads to subsequent adult hypertension, but the mechanisms involved in this developmental programming remain largely unknown. In this study we tested the hypothesis that programmed hypertension in rats is linked to altered renal expression of the glucocorticoid receptor, mineralocorticoid receptor, and 11␤-hydroxysteroid dehydrogenase type 2 and components of the intrarenal and adipose renin-angiotensin system. The interactive effects of a postnatal diet enriched in omega-3 fatty acids, which prevents emergence of the hypertensive phenotype, were also examined. Maternal dexamethasone (0.75 g/mL of drinking water from day 13 to term) markedly increased renal expression of the glucocorticoid receptor in 6-month-old offspring, and this was associated with hypomethylation of the glucocorticoid receptor promoter; renal MR was unaffected. In contrast, maternal dexamethasone reduced renal 11␤-hydroxysteroid dehydrogenase type 2 in offspring, but this effect was prevented by a high omega-3 diet. Consistent with these effects, renal Na/K-ATPase-␣1 was elevated in offspring of dexamethasone-treated mothers, but only in those raised on the standard diet. Maternal dexamethasone also programmed increased expression of renal and adipose angiotensin-converting enzyme and renal renin, but among these changes, only that of renal angiotensin-converting enzyme was prevented by the omega-3 diet. Our data support the hypothesis that programmed hypertension is mediated, in part, by increased renal glucocorticoid sensitivity, with consequent stimulatory effects on Na/K-ATPase-␣1 and intrarenal renin-angiotensin system components. Partial prevention of programmed changes in renal gene expression by postnatal dietary omega-3 fatty acids provides insight into how this intervention prevents hypertension induced by fetal glucocorticoid excess. Key Words: prenatal programming Ⅲ hypertension Ⅲ glucocorticoids Ⅲ 11␤-hydroxysteroid dehydrogenase type 2 Ⅲ renin-angiotensin system Ⅲ kidney Ⅲ omega-3 fatty acids D evelopmental programming is now recognized as a key determinant of the adult phenotype, most notably in relation to regulation of blood pressure, insulin sensitivity, and adiposity. 1 Thus, fetal insults, such as undernutrition or glucocorticoid excess, can lead to adult hypertension and insulin resistance, but the mechanisms underlying such programming outcomes remain largely unknown. 2,3 Moreover, the severity of the programmed phenotype can be either reduced or exacerbated by the postnatal environment. Specifically, adult hypertension programmed by fetal undernutrition is worsened by a hypercaloric diet in postnatal life, 4 whereas we recently reported that hypertension programmed by maternal dexamethasone treatment is prevented when offspring are raised on a diet enriched with omega-3 (n-3) fatty acids. 5 This rescue of the programmed phenotype is consistent with the well-recognized, beneficial effects of dietary n-3 fatty acids in relation to human hypertension. 6 Interestingly, hyperleptinemia ...

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“…37 Indeed, isome-proliferator activated receptors ␣ and ␥ agonists were shown recently to suppress vascular ACE expression in stretozotocin-induced diabetic rats. 38 …”

Section: Ace and Renin Mrna Expression In Renal And Adipose Tissues Omentioning

confidence: 99%

Developmental Programming of Renal Glucocorticoid Sensitivity and the Renin-Angiotensin System

2007

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“…One study has shown that a PPARγ ligand inhibits expression of the NADPH oxidase subunits p22 phox and p47 phox in vitro (19). Another study has shown that PPARγ ligands inhibit NADPH oxidase expression in the streptozotocin-induced diabetic rat aorta in vivo (4). Here, p22 phox expression was significantly reduced in the aortae of telmisartan-treated SHR-SP and sodium-loaded SHR-SP compared with placebo-treated rats, whereas valsartan did not attenuate p22 phox expression.…”

Section: Fig 5 Ace Activities In Wky Rats Placebo (P)- Telmisartamentioning

confidence: 62%

“…Toba et al . ( 4 ) reported that PPAR γ ligands, pioglitazone and bezafibrate, prevent the streptozotocin-induced increase in vascular ACE gene expression and protein content in rats. However, it remains unclear whether or not telmisartan has more effective vascular ACE activity than other ARBs that have no PPAR γ agonistic effect.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Vascular Angiotensin-Converting Enzyme by Telmisartan via the Peroxisome Proliferator-Activated Receptor .GAMMA. Agonistic Property in Rats

Jin

Kimura

Kirimura³

et al. 2007

Hypertens Res

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“…one study found the ACE activity in blood to be related with the ACE I/D genotype, partially due to an increased rate of transcription of the ACE D allele 29) . Recently, Toba et al reported that pioglitazone exerted anti-oxidative and anti-inflammatory effects through the inhibition of ACE expression in the aorta of rats with streptozotocin-induced diabetes 30) . Together with increased expression of the ACE gene and increased renin-angiotensin system (RAS)-induced oxidative stress, pioglitazone may modulate oxidative stress-induced progression of atherosclerosis by acting on the augmented RAS system in subjects with type 2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

Genetic Risk Factors and the Anti-Atherosclerotic Effect of Pioglitazone on Carotid Atherosclerosis of Subjects with Type 2 Diabetes —A Retrospective Study—

Saitou

Osonoi

Kawamori

et al. 2010

JAT

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The direct antioxidative and anti-inflammatory effects of peroxisome proliferator-activated receptors ligands are associated with the inhibition of angiotensin converting enzyme expression in streptozotocin-induced diabetic rat aorta

Cited by 36 publications

References 35 publications

Developmental Programming of Renal Glucocorticoid Sensitivity and the Renin-Angiotensin System

Developmental Programming of Renal Glucocorticoid Sensitivity and the Renin-Angiotensin System

Inhibition of Vascular Angiotensin-Converting Enzyme by Telmisartan via the Peroxisome Proliferator-Activated Receptor .GAMMA. Agonistic Property in Rats

Genetic Risk Factors and the Anti-Atherosclerotic Effect of Pioglitazone on Carotid Atherosclerosis of Subjects with Type 2 Diabetes —A Retrospective Study—

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