Clitoria ternatea L. extract prevents kidney damage by suppressing the Ang II/Nox4/oxidative stress cascade in L-NAME-induced hypertension model of rats

2021 ◽  
pp. 151783
Author(s):  
Benchaporn Saengnak ◽  
Pipatpong Kanla ◽  
Rarinthorn Samrid ◽  
Thewarid Berkban ◽  
Wilaiwan Mothong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Kidney Damage ◽  
Ang Ii ◽  
Clitoria Ternatea ◽  
Induced Hypertension

Abstract 250: 6β-hydroxytestosterone, A Cytochrome P450 1b1-derived Metabolite Of Testosterone, Mediates Increase In Thirst, Renal Dysfunction, And End Organ Damage Associated With Angiotensin II-induced Hypertension In Male Mice

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Ajeeth K Pingili ◽  
Mehmet Kara ◽  
Brett L Jennings ◽  
Anne M Estes ◽  
Kafait U Malik
Keyword(s):  
Oxidative Stress ◽  
Renal Function ◽  
Cytochrome P450 ◽  
Renal Fibrosis ◽  
Organ Damage ◽  
Ang Ii ◽  
Male Mice ◽  
End Organ Damage ◽  
Cytochrome P450 1B1 ◽  
Induced Hypertension

Recently, we showed that 6β-hydroxytestosterone (6β-OHT), a cytochrome P450 1B1 (CYP1B1)-derived metabolite of testosterone, contributes to the development of angiotensin II (Ang II)-induced hypertension and associated cardiovascular pathophysiology. In view of the critical role of Ang II in renal homeostasis and end organ damage, we determined the contribution of 6β-OHT to Ang II actions on water consumption and renal function in male Cyp1b1 +/+ and Cyp1b1 -/- mice. Eight weeks old male Cyp1b1 +/+ and Cyp1b1 -/- intact or castrated mice were injected with 6β-OHT (15 μg/g, i.p. every 3 rd day) or vehicle (DMSO, 50 μl), and infused with Ang II (700 ng/kg/min) or vehicle for 2 weeks. Urine was collected for 24 hours on the final day of experiment. Castration attenuated Ang II-induced increase in water consumption and urine output, proteinuria and decrease in osmolality in both Cyp1b1 +/+ , and Cyp1b1 -/- mice (Table 1). 6β-OHT did not alter Ang II-induced increase in water intake, urine output, proteinuria and decrease in osmolality in Cyp1b1 +/+ mice, but restored these effects of Ang II in Cyp1b1 -/- or castrated mice (Table 1). Cyp1b1 gene disruption or castration prevented Ang II-induced renal fibrosis, inflammation, and oxidative stress. 6β-OHT did not alter Ang II-induced renal fibrosis, inflammation or oxidative stress in Cyp1b1 +/+ mice, however in Cyp1b1 -/- or castrated mice it restored these effects of Ang II. These data suggest that 6β-OHT, contributes to increased thirst, impairment of renal function and end organ damage associated with Ang II-induced hypertension in male mice, and that CYP1B1 could serve as a novel target for the treatment of renal disease and hypertension.

scholarly journals Serelaxin reduces oxidative stress and asymmetric dimethylarginine in angiotensin II-induced hypertension

2014 ◽  
Vol 307 (12) ◽  
pp. F1355-F1362 ◽  
Author(s):  
Jennifer M. Sasser ◽  
Mark W. Cunningham ◽  
Chris Baylis
Keyword(s):  
Oxidative Stress ◽  
Asymmetric Dimethylarginine ◽  
Oxidation Products ◽  
No Oxidation ◽  
Kidney Cortex ◽  
High Dose ◽  
Protective Effects ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Induced Hypertension

Recent findings suggest the therapeutic action of relaxin during hypertension is dependent on nitric oxide synthase (NOS) activation; however, the mechanisms underlying the beneficial effects of relaxin on the NOS system have not been fully elucidated. We hypothesized that the protective effects of relaxin include reducing both oxidative stress and the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA). We examined the effect of Serelaxin [human recombinant relaxin-2 (RLX)] in male Sprague-Dawley rats given high-dose angiotensin (ANG) II (400 ng·kg−1·min−1 sc) for 6 wk or shams. RLX was administered (4 μg/h sc) to half of the rats in each group after 2 wk of ANG II for the remaining 4 wk. ANG II induced hypertension and proteinuria, reduced NO oxidation products (NOx), and increased oxidative stress (NADPH oxidase activity, thiobarbituric acid-reactive substances, and 8-isoprostane excretion) and plasma ADMA. While RLX had no effect on sham rats, RLX attenuated the ANG II-dependent hypertension (165 ± 5 vs. 135 ± 13 mmHg, P < 0.05) and proteinuria at 6 wk (62 ± 6 vs. 41 ± 4 mg·day−1·100 g−1, P < 0.05) and normalized oxidative stress and circulating ADMA, in association with restored NOx excretion and kidney cortex NOx. We found that RLX had no impact on the ADMA-regulatory enzymes protein arginine methyltransferase and dimethylarginine-dimethylaminohydrolase (DDAH). Furthermore, RLX treatment did not increase DDAH activity in kidney cortex or liver. These data suggest that benefits of RLX treatment include reduced ADMA levels and increased NO bioavailability, possibly due to its antioxidant effects.

scholarly journals Neohesperidin Protects Hypertension-induced Endothelial Injury by Intervening Oxidative Stress

2021 ◽  
Author(s):  
Jingsi Zhang ◽  
Yuanshu Hui ◽  
Fengyi Liu ◽  
Qian Yang ◽  
Yi Lu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vascular Inflammation ◽  
Endothelial Damage ◽  
Endothelial Injury ◽  
Vascular Endothelial ◽  
Ang Ii ◽  
Induced Hypertension ◽  
And Oxidative Stress

Abstract Background: Currently, vascular endothelial damage caused by hypertension is one of the major health challenges facing countries around the world. Neohesperidin has been shown to play an important role in tumorigenesis and tumorigenesis, cardiac hypertrophy and remodeling, and oxidative stress. However, whether Nehesperidin plays an important role in endothelial injury induced by hypertension has not been clarified.Results: In this study, Angiotensin II was used to induce hypertension in mice. Blood pressure and vasoconstrictor function were measured, vascular thickness and fibrosis were detected by H&E and Masson tricolor staining, vascular inflammation was detected by immunofluorescence, oxidative stress was detected by DHE staining, and markers such as fibrosis, hypertrophy and oxidative stress were detected by qPCR. At the same time, we observed the effect of Nehesperidin on Ang II-induced HUVECs. The results showed that neohesperidin can significantly inhibit Ang II-induced hypertension, vascular thickness, fibrosis, oxidative stress and inflammation in vivo and in vitro. Conclusions: The results suggested that Nehesperidin could act as an antioxidant to significantly inhibit Ang II-induced hypertension and endothelial injury in HUVECs in mice by inhibiting oxidative stress response.

Abstract P140: Epigenetic Regulation of Nox4 in Hypertension-induced Injury in Aged Kidney

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Lu Ren ◽  
Biswa Das Purkayastha ◽  
Utpal Sen ◽  
Sathnur Pushpakumar
Keyword(s):  
Oxidative Stress ◽  
Protein Expression ◽  
Epigenetic Regulation ◽  
Dna Methyltransferases ◽  
Kidney Damage ◽  
Epigenetic Mechanism ◽  
Current Evidence ◽  
Ang Ii ◽  
Aged Mice ◽  
Aged Kidney

The prevalence of hypertension increases with age. At the cellular level, oxidative stress is a major contributing factor to the pathogenesis of hypertension-induced kidney damage. The nicotinamide adenine dinucleotide phosphate (NADPH) family is one of the major sources of reactive oxygen species generation in the body. Although the isoform, NADPH oxidase 4 (Nox4) is highly expressed in the kidney, its role in kidney diseases remains controversial as both pathogenic and protective effects have been described. In addition, its role in hypertension-induced kidney damage in aging remains unexplored. Current evidence supports the involvement of epigenetics in oxidative stress. The aim of the present study was to investigate the role of Nox4 in Ang-II induced kidney damage in aged mice and the potential role for epigenetic regulation. Wild type (WT, C57BL/6J) mice aged 12-14 wk and 75-78 wk were used in this study and treated with Ang-II (1000 ng/kg/min) for 4 weeks. Control mice received saline infusion. Blood pressure (BP) was measured twice weekly. Aged mice exhibited higher mean BP than young mice after Ang-II treatment (135.76±4.8 vs. 118.7±12.28 mmHg) and decreased renal vascular density on barium angiography. Dihydroethidium staining revealed increased oxidative stress in hypertensive kidney of aged mice. In the aged kidney, protein expression of mitochondrial antioxidant enzymes, manganese superoxide dismutase and catalase was decreased by > 2-fold compared to young, and decreased further after Ang-II infusion. The renal sensors of energy and redox state, SIRT1 and SIRT3, showed similar decrease in aged kidney compared to young kidney in response to Ang-II. Nox4 and p22 phox protein expression was upregulated in the hypertensive kidneys of aged mice. The epigenetic mechanism involving DNA methylation showed increased DNA methyltransferases, DNMT1, 3a and 3b in the aged kidney. Following Ang-II, the aged kidney showed further increase of DNMT1 and 3a and a decrease in DNMT3b. Conclusion: Endogenous expression of Nox4 is upregulated in hypertensive kidney and is associated with alteration of DNA methyltransferases suggesting epigenetic regulation of oxidative stress in aged mice.

scholarly journals Prevention of aortic fibrosis by N-acetyl-seryl-aspartyl-lysyl-proline in angiotensin II-induced hypertension

2008 ◽  
Vol 295 (3) ◽  
pp. H1253-H1261 ◽  
Author(s):  
Chun-Xia Lin ◽  
Nour-Eddine Rhaleb ◽  
Xiao-Ping Yang ◽  
Tang-Dong Liao ◽  
Martin A. D'Ambrosio ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mrna Expression ◽  
Macrophage Infiltration ◽  
Ang Ii ◽  
Antifibrotic Effect ◽  
Smad2 Phosphorylation ◽  
Induced Hypertension ◽  
Anti Inflammatory ◽  
Pkc Activation ◽  
Tgf Β1

Fibrosis is an important component of large conduit artery disease in hypertension. The endogenous tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) has anti-inflammatory and antifibrotic effects in the heart and kidney. However, it is not known whether Ac-SDKP has an anti-inflammatory and antifibrotic effect on conduit arteries such as the aorta. We hypothesize that in ANG II-induced hypertension Ac-SDKP prevents aortic fibrosis and that this effect is associated with decreased protein kinase C (PKC) activation, leading to reduced oxidative stress and inflammation and a decrease in the profibrotic cytokine transforming growth factor-β1 (TGF-β1) and phosphorylation of its second messenger Smad2. To test this hypothesis we used rats with ANG II-induced hypertension and treated them with either vehicle or Ac-SDKP. In this hypertensive model we found an increased collagen deposition and collagen type I and III mRNA expression in the aorta. These changes were associated with increased PKC activation, oxidative stress, intercellular adhesion molecule (ICAM)-1 mRNA expression, and macrophage infiltration. TGF-β1 expression and Smad2 phosphorylation also increased. Ac-SDKP prevented these effects without decreasing blood pressure or aortic hypertrophy. Ac-SDKP also enhanced expression of inhibitory Smad7. These data indicate that in ANG II-induced hypertension Ac-SDKP has an aortic antifibrotic effect. This effect may be due in part to inhibition of PKC activation, which in turn could reduce oxidative stress, ICAM-1 expression, and macrophage infiltration. Part of the effect of Ac-SDKP could also be due to reduced expression of the profibrotic cytokine TGF-β1 and inhibition of Smad2 phosphorylation.

Gene expression reveals vulnerability to oxidative stress and interstitial fibrosis of renal outer medulla to nonhypertensive elevations of ANG II

2003 ◽  
Vol 284 (5) ◽  
pp. R1219-R1230 ◽  
Author(s):  
Baozhi Yuan ◽  
Mingyu Liang ◽  
Zhizhang Yang ◽  
Elizabeth Rute ◽  
Norman Taylor ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Western Blot ◽  
Renal Injury ◽  
Interstitial Fibrosis ◽  
Control Period ◽  
Renal Medulla ◽  
Differentially Expressed ◽  
Ang Ii ◽  
Outer Medulla ◽  
Renal Outer Medulla

The present study was designed to determine whether nonhypertensive elevations of plasma ANG II would modify the expression of genes involved in renal injury that could influence oxidative stress and extracellular matrix formation in the renal medulla using microarray, Northern, and Western blot techniques. Sprague-Dawley rats were infused intravenously with either ANG II (5 ng · kg−1 · min−1) or vehicle for 7 days ( n = 6/group). Mean arterial pressure averaged 110 ± 0.6 mmHg during the control period and 113 ± 0.4 mmHg after ANG II. The mRNA of 1,751 genes (∼80% of all currently known rat genes) that was differentially expressed (ANG II vs. saline) in renal outer and inner medulla was determined. The results of 12 hybridizations indicated that in response to ANG II, 11 genes were upregulated and 25 were downregulated in the outer medulla, while 11 were upregulated and 13 were downregulated in the inner medulla. These differentially expressed genes, most of which were not known previously to be affected by ANG II in the renal medulla, were found to group into eight physiological pathways known to influence renal injury and kidney function. Particularly, expression of several genes would be expected to increase oxidative stress and interstitial fibrosis in the outer medulla. Western blot analyses confirmed increased expression of transforming growth factor-β1 and collagen type IV proteins in the outer medulla. Results demonstrate that nonhypertensive elevations of plasma ANG II can significantly alter the expression of a variety of genes in the renal outer medulla and suggested the vulnerability of the renal outer medulla to the injurious effect of ANG II.

Vascular and Antioxidant Effects of an Aqueous Mentha cordifolia Extract in Experimental NG-Nitro-L-arginine Methyl Ester-Induced Hypertension

2014 ◽  
Vol 69 (1-2) ◽  
pp. 35-45 ◽  
Author(s):  
Poungrat Pakdeechote ◽  
Parichat Prachaney ◽  
Warinee Berkban ◽  
Upa Kukongviriyapan ◽  
Veerapol Kukongviriyapan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Methyl Ester ◽  
Thoracic Aorta ◽  
Wall Thickness ◽  
Vascular Remodeling ◽  
Oxidative Stress Markers ◽  
Sectional Area ◽  
Cross Sectional ◽  
Stress Markers ◽  
Induced Hypertension

The effect of an aqueous Mentha cordifolia (MC) extract on the haemodynamic status, vascular remodeling, function, and oxidative status in NG-nitro-L-arginine methyl ester (L-NAME)-induced hypertension was investigated. Male Sprague-Dawley rats were given L-NAME [50 mg/(kg body weight (BW) d)] in their drinking water for 5 weeks and were treated by intragastric administration with the MC extract [200 mg/(kgBWd)] for 2 consecutive weeks. Quercetin [25 mg/(kg BW d)] was used as a positive control. The effects of the MC extract on the haemodynamic status, thoracic aortic wall thickness, and oxidative stress markers were determined, and the vasorelaxant activity of the MC extract was tested in isolated mesenteric vascular beds in rats. Significant increases in the mean arterial pressure (MAP), heart rate (HR), hind limb vascular resistance (HVR), wall thickness, and cross-sectional area of the thoracic aorta, as well as oxidative stress markers were found in the LNAME- treated group compared to the control (P<0.05). MAP, HVR, wall thickness, cross-sectional area of the thoracic aorta, plasma malondialdehyde (MDA), and vascular superoxide anion production were significantly reduced in L-NAME hypersensitive rats treated with the MC extract or quercetin. Furthermore, the MC extract induced vasorelaxation in the pre-constricted mesenteric vascular bed with intact and denuded endothelium of normotensive and hypertensive rats. Our results suggest that the MC extract exhibits an antihypertensive effect via its antioxidant capacity, vasodilator property, and reduced vascular remodeling.

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