Abstract 135: Obesity Accelerates the Deterioration of Renal Function in Developmental Programming of Hypertension. Role of Angiotensin Ii and Oxidative Stress

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Antonio Tapia ◽  
Juan M Moreno ◽  
Maria T Llinas ◽  
F. Javier Salazar
Keyword(s):  
Oxidative Stress ◽  
Renal Function ◽  
Angiotensin Ii ◽  
Perinatal Period ◽  
Developmental Programming ◽  
Ang Ii ◽  
Obese Rats ◽  
Renal Vascular ◽  
And Oxidative Stress

Numerous studies have shown gender-dependent differences in the deterioration of renal function in models of developmental programming of hypertension (DPH). It is also known that obesity is associated to changes in renal function and that both angiotensin II (Ang II) and oxidative stress are involved in the renal alterations that occur in obesity and in animals with DPH. The main objectives were to examine whether the increment of arterial pressure (AP) and the deterioration of renal function are accelerated as a consequence of obesity in SD rats with DPH; whether these changes are gender-dependent; and to evaluate the role of Ang II and oxidative stress in these AP and renal function changes. A high fat diet (60%) was given during the first 4 months of age and DPH was induced by an AT receptor antagonist during nephrogenic period (ARAnp). Systolic AP (mmHg) was greater (P<0.05) in ARAnp-obese rats (167 ± 3 in ♂; 146 ± 4 in ♀) than in ARAnp (155 ± 3 in ♂; 137 ± 3 in ♀); obese (147 ± 2 in ♂; 137 ± 2 in ♀) or control (127 ± 1 in ♂; 119 ± 2 in ♀) rats. Three days administration of candesartan (7 mg/kg/day) led to a decrease in AP that was greater (P<0.05) in ARAnp-obese rats (55 ± 3 in ♂; 45 ± 4 in ♀) than in ARAnp (40 ± 3 in ♂; 37 ± 4 in ♀); obese (38 ± 4 in ♂; 27 ± 4 in ♀) or control (12 ± 2 in ♂; 14 ± 3 in ♀) rats. The acute Ang II infusion (30 ng/kg/min) induced an increase in renal vascular resistance (mmHg/ml/min/gr kw) that was also greater in ARAnp-obese rats (217 ± 45% in ♂; 145 ± 38% in ♀) than in ARAnp (103 ± 9% in ♂; 97 ± 8% in ♀); obese (106 ± 14% in ♂; 106 ± 17 in ♀) or control (51 ± 7% in ♂; 51 ± 10% in ♀) rats. The response to candesartan or Ang II infusion in ARAnp-obese rats was gender-dependent and may be explained by an enhanced oxidative stress. The expression of P67phox in the renal cortex was greater (P<0.05) in ARAnp-obese rats (3,00 ± 0,05 in ♂; 2,60 ± 0,04 in ♀) than in ARAnp (1,16 ± 0,04 in ♂; 1,66 ± 0,03 in ♀); obese (0,94 ± 0,06 in ♂; 1,02 ± 0,02 in ♀) or control (1,00 ± 0,02 in ♂; 1,02 ± 0,023 in ♀) rats. The results of this study suggest that obesity at an early age enhances the hypertension and accelerates the deterioration of renal function that occurs when cardiovascular disease is programmed during the perinatal period. It is also shown that Ang II and oxidative stress seems to play an important role in these AP and renal function changes.

Abstract 1476: Angiotensin II Induced Hypertrophic Response And Oxidative Stress Is Attenuated In Mice Lacking The Gene For Tnf-α

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Srinivas Sriramula ◽  
Nithya Mariappan ◽  
Elizabeth McILwain ◽  
Joseph Francis
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Collagen Type ◽  
Resonance Spectroscopy ◽  
Type I ◽  
Ang Ii ◽  
Hypertrophic Response ◽  
Tnf Α ◽  
And Oxidative Stress

Tumor necrosis factor-alpha (TNF-α) and angiotensin II (Ang II) play an important role in the pathophysiology of cardiovascular disease in part by inducing the cardiac hypertrophic response and oxidative stress. Recently we demonstrated that angiotensin induced hypertensive response is attenuated in mice lacking the gene for TNF-α. In this study, we examined whether Ang II induced cardiac hypertrophy and increased oxidative stress is mediated through TNF-α. Methods and results: Male TNF-α (−/−) and age matched control (WT) mice were subcutaneously implanted with osmotic minipumps containing Ang II (1 μg/kg/min) or saline for 14 days. Human recombinant TNF-α was injected in one group of TNF-α (−/−) mice (10 μg/kg/day) for 14 days. In WT+Ang mice, a temporal increase in blood pressure was observed during the study as measured by radio telemetry transmitters. At the end of the study, echocardiography revealed an increase in thickness and dimensions of left ventricle (LV) and decreased fractional shortening (%FS) in WT+Ang mice. Real time RT-PCR showed that Ang II- infusion resulted in an increase in heart/bodyweight ratio and of cardiac hypertrophy markers ANP and BNP, and profibrotic genes Collagen Type I, Collagen Type II, and TGF-β in WT mice. Electron Spin resonance spectroscopy revealed an increase in total ROS, superoxide and peroxynitrite in the WT+ANG mice when compared to control WT mice. However, these changes were all attenuated in TNF-α (−/−)+Ang mice. Ang II infusion also increased significantly the mRNA expression of gp91Phox, NOX-1, NOX-4 and AT1R in the LV of WT mice, but not in TNF-α (−/−) mice. Interestingly, injection of TNF-α in the TNF-α (−/−) mice, treated with Ang II resulted in increased cardiac hypertrophy and oxidative stress. Conclusions: Findings from the present study suggest that TNF-α plays an important role in the development of cardiac hypertrophy and oxidative stress in Ang II-induced hypertension.

Abstract 7: Angiotensin II Type 2 Receptor Deficiency Increases Renal ACE/ACE2 Ratio-Ang II-AT1R Expression In Male but not in Female Mice

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Quaisar Ali ◽  
Yonnie Wu ◽  
Tadashi Inagami ◽  
Tahir Hussain
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Angiotensin Ii ◽  
Renin Activity ◽  
Ang Ii ◽  
Male And Female ◽  
Female Mice ◽  
Gender Specific

Angiotensin II acting via Angiotensin II type 2 receptors (AT2Rs) is believed to be protective against blood pressure increase and affects renal function under pathophysiological condition. Recently we have observed that stimulation of AT2Rs in male obese Zucker rats has shifted the two opposing arms of renin angiotensin system (RAS) i.e. ACE-Ang II-AT1 vs ACE2/Ang-(1-7)-Mas. Evidence suggests that estrogen regulates RAS, including AT2R in female mice. We hypothesized that AT2R has a gender specific regulation of RAS. In the present study, we investigated the role of AT2Rs in regulating RAS components in male and female mice. Kidney cortex from AT2R knockout (AT2RKO) male and female mice and wild type (WT) with similar background (C57BL/6) of 20 weeks of age were used in the study. The cortical ACE expression (ng ACE/μg tissue) was significantly increased in AT2RKO mice (3±0.02) compared to WT males (1.9±0.02). LC/MS analysis of cortical tissue revealed that Ang II was also significantly increased in AT2RKO mice (WT: 31±3, AT2RKO: 47±3 fmoles/mg tissue). Deletion of AT2R significantly increased AT1R (204%, 204 of 100) expression and had no effect on renin activity compared to WT males. The cortical expression of ACE2 activity (WT: 113±8, AT2RKO: 40±11, RFU/min), Ang-(1-7) levels (WT: 7.3±1.4, AT2RKO: 3±0.8 fmoles/mg tissue) and Mas receptor (AT2RKO: 54±15, % of WT) was significantly decreased in AT2RKO males compared to WT. The cortical expression of the AT2R and MasR was 2-fold greater in WT females compared to WT male. The renin activity (WT: 32±2, AT2RKO: 21±0.3, RFU/min) and MasR expression (WT: 187.5±55, AT2KO: 47±9) was significantly decreased in AT2RKO females compared to the female WT. Interestingly, Ang-(1-7) level (WT: 5.7±0.7, AT2RKO 2.6±0.7 fmoles/mg tissue) was decreased but no changes in ACE or ACE2 activity was observed in AT2KO females compared to their WT, suggesting a role of non-ACE2 pathway. This study suggests that AT2R regulates ACE/ACE2 ratio-Ang II-AT1R expression negatively only in males, whereas in females, it regulates Ang-(1-7) potentially via non-ACE2 pathway. Such changes indicate a gender specific mechanisms potentially associated with AT2R-mediated regulation of renal function and blood pressure control.

Angiotensin-induced defects in renal oxygenation: role of oxidative stress

2005 ◽  
Vol 288 (1) ◽  
pp. H22-H28 ◽  
Author(s):  
William J. Welch ◽  
Jonathan Blau ◽  
Hui Xie ◽  
Tina Chabrashvili ◽  
Christopher S. Wilcox
Keyword(s):  
Angiotensin Ii ◽  
Nadph Oxidase ◽  
Glass Electrode ◽  
Ang Ii ◽  
Renal Vasoconstriction ◽  
Mrna And Protein Expression ◽  
Renal Vascular ◽  
Induced Defects ◽  
Renal Oxygen

We tested the hypothesis that superoxide anion (O2−·) generated in the kidney by prolonged angiotensin II (ANG II) reduces renal cortical Po2 and the use of O2 for tubular sodium transport (TNa:QO2). Groups ( n = 8–11) of rats received angiotensin II (ANG II, 200 ng·kg−1·min−1 sc) or vehicle for 2 wk with concurrent infusions of a permeant nitroxide SOD mimetic 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (Tempol, 200 nmol·kg−1·min−1) or vehicle. Rats were studied under anesthesia with measurements of renal oxygen usage and Po2 in the cortex and tubules with a glass electrode. Compared with vehicle, ANG II increased mean arterial pressure (107 ± 4 vs. 146 ± 6 mmHg; P < 0.001), renal vascular resistance (42 ± 3 vs. 65 ± 7 mmHg·ml−1·min−1·100 g−1; P < 0.001), renal cortical NADPH oxidase activity (2.3 ± 0.2 vs. 3.6 ± 0.4 nmol O2−··min−1·mg−1 protein; P < 0.05), mRNA and protein expression for p22 phox (2.1- and 1.8-fold respectively; P < 0.05) and reduced the mRNA for extracellular (EC)-SOD (−1.8 fold; P < 0.05). ANG II reduced the Po2 in the proximal tubule (39 ± 1 vs. 34 ± 2 mmHg; P < 0.05) and throughout the cortex and reduced the TNa:QO2 (17 ± 1 vs. 9 ± 2 μmol/μmol; P < 0.001). Tempol blunted or prevented all these effects of ANG II. The effects of prolonged ANG II to cause hypertension, renal vasoconstriction, renal cortical hypoxia, and reduced efficiency of O2 usage for Na+ transport, activation of NADPH oxidase, increased expression of p22 phox, and reduced expression of EC-SOD can be ascribed to O2−· generation because they are prevented by an SOD mimetic.

Role of oxidative stress in angiotensin II-induced enhanced expression of Giα proteins and adenylyl cyclase signaling in A10 vascular smooth muscle cells

2007 ◽  
Vol 292 (4) ◽  
pp. H1922-H1930 ◽  
Author(s):  
Yuan Li ◽  
Georgios Lappas ◽  
Madhu B. Anand-Srivastava
Keyword(s):  
Oxidative Stress ◽  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Adenylyl Cyclase ◽  
Vascular Smooth Muscle Cells ◽  
Ang Ii ◽  
Enhanced Expression

We have previously reported that angiotensin II (ANG II) treatment of A10 vascular smooth muscle cells (VSMCs) increased inhibitory G proteins (Gi protein) expression and associated adenylyl cyclase signaling which was attributed to the enhanced MAP kinase activity. Since ANG II has been shown to increase oxidative stress, we investigated the role of oxidative stress in ANG II-induced enhanced expression of Giα proteins and examined the effects of antioxidants on ANG II-induced enhanced expression of Giα proteins and associated adenylyl cyclase signaling in A10 VSMCs. ANG II treatment of A10 VSMCs enhanced the production of O2− and the expression of Nox4 and P47phox, different subunits of NADPH oxidase, which were attenuated toward control levels by diphenyleneiodonium (DPI). In addition, ANG II augmented the expression of Giα-2 and Giα-3 proteins in a concentration- and time-dependent manner; the maximal increase in the expression of Giα was observed at 1 to 2 h and at 0.1–1.0 μM. The enhanced expression of Giα-2 and Giα-3 proteins was restored to control levels by antioxidants such as N-acetyl-l-cysteine, α-tocopherol, DPI, and apocynin. In addition, ANG II also enhanced the ERK1/2 phosphorylation that was restored to control levels by DPI. Furthermore, the inhibition of forskolin-stimulated adenylyl cyclase activity by low concentrations of 5′- O-(3-triotriphosphate) (receptor-independent Gi functions) and ANG II-, des(Glu18,Ser19,Glu20,Leu21,Gly22)atrial natriuretic peptide4-23-NH2 (natriuretic peptide receptor-C agonist), and oxotremorine-mediated inhibitions of adenylyl cyclase (receptor-dependent functions) that were augmented in ANG II-treated VSMCs was also restored to control levels by antioxidant treatments. In addition, Gsα-mediated diminished stimulation of adenylyl cyclase by stimulatory hormones in ANG II-treated cells was also restored to control levels by DPI. These results suggest that ANG II-induced enhanced levels of Giα proteins and associated functions in VSMCs may be attributed to the ANG II-induced enhanced oxidative stress, which exerts its effects through mitogen-activated protein kinase signaling pathway.

scholarly journals Renal Vascular Response to Angiotensin II Administration in Two Kidneys-One Clip Hypertensive Rats Treated with High Dose of Estradiol: The Role of Mas Receptor

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Samira Choopani ◽  
Mehdi Nematbakhsh
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Ovariectomized Rats ◽  
Ang Ii ◽  
Vascular Response ◽  
Hypertensive Rats ◽  
Vascular Responses ◽  
Mas Receptor ◽  
Renal Vascular

Backgrounds. High blood pressure is one of the most important causes of death around the world. The renin-angiotensin system (RAS) and estradiol are two important items that regulate arterial blood pressure in women. However, hypertension, RAS, and sex hormone estradiol may influence renal vascular responses. This study was designed to determine the role of Mas receptor (MasR) on renal vascular response to angiotensin II (Ang II) administration in two kidneys-one clip (2K1C) hypertensive rats treated with estradiol. Method. The ovariectomized rats were subjected to 2K1C or non-2K1C and simultaneously treated with estradiol (500 μg/kg/weekly) or placebo for a period of 4 weeks. Subsequently, under anesthesia, renal vascular responses to graded doses of Ang II administration with MasR blockade (A779) or its vehicle were determined. Results. A779 or its vehicle did not alter mean arterial pressure (MAP), renal perfusion pressure (RPP), and renal blood flow (RBF). However, in non-2K1C rats, Ang II infusion decreased RBF and increased renal vascular resistance (RVR) responses in a dose-related manner ( P treat < 0.0001 ). The greatest responses were found in ovariectomized estradiol-treated rats that received A779 ( P group < 0.05 ) in non-2K1C rats. Such findings were not detected in 2K1C hypertensive rats. For example, in estradiol-treated rats that received A779, at 1000 ng/kg/min of Ang II infusion, RBF reduced from 1.6 ± 0.2 to 0.89 ± 0.19  ml/min in non-2K1C rats, and it reduced from 1.6 ± 0.2 to 1.2 ± 0.2  ml/min in 2K1C rats. Conclusion. Hypertension induced by 2K1C may attenuate the role of A779 and estradiol in renal vascular responses to Ang II infusion. Perhaps, this response can be explained by the reduction of Ang II type 1 receptor (AT1R) expression in the 2K1C hypertensive rats.

scholarly journals Role of NADPH Oxidase in the Vascular Hypertrophic and Oxidative Stress Response to Angiotensin II in Mice

2001 ◽  
Vol 88 (9) ◽  
pp. 947-953 ◽  
Author(s):  
Hui Di Wang ◽  
Shanqin Xu ◽  
Douglas G. Johns ◽  
Yue Du ◽  
Mark T. Quinn ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Angiotensin Ii ◽  
Nadph Oxidase ◽  
Oxidative Stress Response ◽  
And Oxidative Stress

Abstract 3542: Role of Mitochondrial Oxidative Stress in Angiotensin II Mediated Hypertension

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Anna E Dikalova ◽  
Alfiya T Bikineyeva ◽  
David G Harrison ◽  
Sergey I Dikalov
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Ii ◽  
Heart Association ◽  
Ang Ii ◽  
Mitochondrial Oxidative Stress ◽  
Bovine Endothelial Cells ◽  
Mouse Aorta ◽  
Dose Dependent ◽  
Dose Dependent Effect

Oxidative stress is strongly implicated in the pathogenesis of hypertension; however, the role of mitochondrial oxidative stress is not clear. We have investigated the role of mitochondria in endothelial dysfunction and hypetention using cultured bovine endothelial cells (BAECs) and mice infused with angiotensin II (AngII). Production of O 2 •− was measured by dihydroethidium and HPLC. Nitric oxide and H 2 O 2 were detected by ESR. Sytolic blood presure was measured in mice infused with saline, AngII (0.7mg/kg/day), AngII plus mitochondria targeted antioxidant mitoTEMPO or non-targeted antioxidant TEMPOL (50 μg/kg/day). AngII significantly increased mitochondrial H 2 O 2 . MitoTEMPO blocked AngII-induced oxidative stress and restored NO • production in BAECs and mouse aorta. Supplementation of BAECs with malonate, inhibitor of complex II, or rotenone abolished AngII induced oxidative stress. Interestingly, inhibition of mitochondrial oxidative stress decreased the activity of NADPH oxidases. Co-infusion of mitoTEMPO with AngII significantly attenuated the increase in the blood pressure by 30-mm Hg (Fig. 1 ), while i.p. injection to hypertensive mice decreased the blood presure by 20-mm Hg. We suggest that mitoTEMPO can be used as an effective inhibitor of the oxidative stress induced by Ang II as well as an antihypertensive agent and, thereby, can be effective in ameliorating hypertension-related nephrosclerosis, diabetic nephropathy, or atherosclerosis. Figure 1. (A) Attenuation of hypertensive effect of Ang II in C57Blk/6 mice by co-infusion of mitoTEMPO. (B) Dose dependent effect of mitoTEMPO (50, 150 and 500 μg/kg/day) after 14-days of Ang II and drug administration. This research has received full or partial funding support from the American Heart Association, AHA National Center.

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