scholarly journals Angiotensin II contributes to glomerular hyperfiltration in diabetic rats independently of adenosine type I receptors

2013 ◽  
Vol 304 (5) ◽  
pp. F614-F622 ◽  
Author(s):  
Daniela Patinha ◽  
Angelica Fasching ◽  
Dora Pinho ◽  
António Albino-Teixeira ◽  
Manuela Morato ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Receptor Antagonist ◽  
Diabetic Rats ◽  
Tubular Function ◽  
Type I ◽  
Ang Ii ◽  
Baseline Blood Pressure ◽  
Pronounced Increase ◽  
Streptozotocin Diabetic Rats ◽  
Renal Vascular

Increased angiotensin II (ANG II) or adenosine can potentiate each other in the regulation of renal hemodynamics and tubular function. Diabetes is characterized by hyperfiltration, yet the roles of ANG II and adenosine receptors for controlling baseline renal blood flow (RBF) or tubular Na+ handling in diabetes is presently unknown. Accordingly, the changes in their functions were investigated in control and 2-wk streptozotocin-diabetic rats after intrarenal infusion of the ANG II AT1 receptor antagonist candesartan, the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), or their combination. Compared with controls, the baseline blood pressure, RBF, and renal vascular resistance (RVR) were similar in diabetics, whereas the glomerular filtration rate (GFR) and filtration fraction (FF) were increased. Candesartan, DPCPX, or the combination increased RBF and decreased RVR similarly in all groups. In controls, the GFR was increased by DPCPX, but in diabetics, it was decreased by candesartan. The FF was decreased by candesartan and DPCPX, independently. DPCPX caused the most pronounced increase in fractional Na+ excretion in both controls and diabetics, whereas candesartan or the combination only affected fractional Li+ excretion in diabetics. These results suggest that RBF, via a unifying mechanism, and tubular function are under strict tonic control of both ANG II and adenosine in both control and diabetic kidneys. Furthermore, increased vascular AT1 receptor activity is a contribution to diabetes-induced hyperfiltration independent of any effect of adenosine A1 receptors.

scholarly journals Mitochondrial angiotensin II receptors regulate oxygen consumption in kidney mitochondria from healthy and type 1 diabetic rats

2020 ◽  
Vol 318 (3) ◽  
pp. F683-F688 ◽  
Author(s):  
Malou Friederich-Persson ◽  
Patrik Persson
Keyword(s):  
Nitric Oxide ◽  
Oxygen Consumption ◽  
Angiotensin Ii ◽  
Receptor Antagonist ◽  
Diabetic Rats ◽  
Kidney Cortex ◽  
Ang Ii ◽  
Kidney Mitochondria ◽  
Receptor Inhibition

Exaggerated activation of the renin-angiotensin-aldosterone system (RAAS) is a key feature in diseases such as hypertension, diabetes, and chronic kidney disease. Recently, an intracellular RAAS was demonstrated with angiotensin II (ANG II) type 1 (AT1) and type 2 (AT2) receptors expressed in nuclei and mitochondria. Diabetes is associated with both mitochondrial dysfunction and increased intracellular ANG II concentration in the kidney cortex. The present study investigated the role of ANG II signaling in kidney cortex mitochondria isolated from control and streptozotocin-induced diabetic rats. Mitochondrial oxygen consumption was evaluated after addition of ANG II alone or after preincubation with candesartan (AT1 receptor antagonist), PD-123319 (AT2 receptor antagonist), or the two in combination. ANG II binds to only mitochondrial AT2 receptors in control rats and both AT1 receptors and AT2 receptors in diabetic rats. ANG II decreased oxygen consumption in mitochondria from both control and diabetic rats. ANG II response was reversed to increased oxygen consumption by the nitric oxide synthase inhibitor N-nitro-l-arginine methyl ester. AT1 receptor inhibition did not affect the response to ANG II, whereas AT2 receptor inhibition abolished the response in mitochondria from control rats and reversed the response to increased oxygen consumption through superoxide-induced mitochondrial uncoupling in mitochondria from diabetic rats. ANG II decrease mitochondrial respiration via AT2 receptor-mediated nitric oxide release in both control and diabetic rats. AT1 receptors do not regulate mitochondria function in control rats, whereas ANG II via AT1 receptors increase mitochondria leak respiration in diabetic animals.

scholarly journals Enhanced angiotensin II-mediated central sympathoexcitation in streptozotocin-induced diabetes: role of superoxide anion

2011 ◽  
Vol 300 (2) ◽  
pp. R311-R320 ◽  
Author(s):  
Kaushik P. Patel ◽  
William G. Mayhan ◽  
Keshore R. Bidasee ◽  
Hong Zheng
Keyword(s):  
Angiotensin Ii ◽  
Protein Expression ◽  
Superoxide Anion ◽  
Receptor Activation ◽  
Diabetic Rats ◽  
Type I ◽  
Ang Ii ◽  
Mrna And Protein Expression ◽  
The Central Nervous System ◽  
Streptozotocin Induced Diabetes

Studies have shown that the superoxide mechanism is involved in angiotensin II (ANG II) signaling in the central nervous system. We hypothesized that ANG II activates sympathetic outflow by stimulation of superoxide anion in the paraventricular nucleus (PVN) of streptozotocin (STZ)-induced diabetic rats. In α-chloralose- and urethane-anesthetized rats, microinjection of ANG II into the PVN (50, 100, and 200 pmol) produced dose-dependent increases in renal sympathetic nerve activity (RSNA), arterial pressure (AP), and heart rate (HR) in control and STZ-induced diabetic rats. There was a potentiation of the increase in RSNA (35.0 ± 5.0 vs. 23.0 ± 4.3%, P < 0.05), AP, and HR due to ANG II type I (AT1) receptor activation in diabetic rats compared with control rats. Blocking endogenous AT1 receptors within the PVN with AT1 receptor antagonist losartan produced significantly greater decreases in RSNA, AP, and HR in diabetic rats compared with control rats. Concomitantly, there were significant increases in mRNA and protein expression of AT1 receptor with increased superoxide levels and expression of NAD(P)H oxidase subunits p22phox, p47phox, and p67phox in the PVN of rats with diabetes. Pretreatment with losartan (10 mg·kg−1·day−1 in drinking water for 3 wk) significantly reduced protein expression of NAD(P)H oxidase subunits (p22phox and p47phox) in the PVN of diabetic rats. Pretreatment with adenoviral vector-mediated overexpression of human cytoplasmic superoxide dismutase (AdCuZnSOD) within the PVN attenuated the increased central responses to ANG II in diabetes (RSNA: 20.4 ± 0.7 vs. 27.7 ± 2.1%, n = 6, P < 0.05). These data support the concept that superoxide anion contributes to an enhanced ANG II-mediated signaling in the PVN involved with the exaggerated sympathoexcitation in diabetes.

Angiotensin II and endothelin-1 augment the vascular complications of diabetes via JAK2 activation

2007 ◽  
Vol 293 (2) ◽  
pp. H1291-H1299 ◽  
Author(s):  
Amy K. L. Banes-Berceli ◽  
Pimonrat Ketsawatsomkron ◽  
Safia Ogbi ◽  
Bela Patel ◽  
David M. Pollock ◽  
...  
Keyword(s):  
Drinking Water ◽  
Angiotensin Ii ◽  
Receptor Antagonist ◽  
Vascular Complications ◽  
Diabetic Rats ◽  
Ang Ii ◽  
Endothelin 1 ◽  
Endothelium Dependent Relaxation ◽  
Stat Pathway

The JAK/STAT pathway is activated in vitro by angiotensin II (ANG II) and endothelin-1 (ET-1), which are implicated in the development of diabetic complications. We hypothesized that ANG II and ET-1 activate the JAK/STAT pathway in vivo to participate in the development of diabetic vascular complications. Using male Sprague-Dawley rats, we performed a time course study [ days 7, 14, and 28 after streptozotocin (STZ) injection] to determine changes in phosphorylation of JAK2, STAT1, and STAT3 in thoracic aorta using standard Western blot techniques. On day 7 there was no change in phosphorylation of JAK2, STAT1, and STAT3. Phosphorylation of JAK2, STAT1, and STAT3 was significantly increased on days 14 and 28 and was inhibited by treatment with candesartan (AT1 receptor antagonist, 10 mg·kg−1·day−1 orally in drinking water), atrasentan (ETA receptor antagonist, 10 mg·kg−1·day−1 orally in drinking water), and AG-490 (JAK2 inhibitor, 5 mg·kg−1·day−1 intraperitoneally). On day 28, treatment with all inhibitors prevented the significant increase in systolic blood pressure (SBP; tail cuff) of STZ-induced diabetic rats (SBP: 157 ± 9.0, 130 ± 3.3, 128 ± 6.8, and 131 ± 10.4 mmHg in STZ, STZ-candesartan, STZ-atrasentan, and STZ-AG-490 rats, respectively). In isolated tissue bath studies, diabetic rats displayed impaired endothelium-dependent relaxation in aorta (maximal relaxation: 95.3 ± 3.0, 92.6 ± 7.4, 76.9 ± 12.1, and 38.3 ± 13.1% in sham, sham + AG-490, STZ + AG-490, and STZ rats, respectively). Treatment of rats with AG-490 restored endothelium-dependent relaxation in aorta from diabetic rats at 14 and 28 days of treatment. These results demonstrate that JAK2 activation in vivo participates in the development of vascular complications associated with STZ-induced diabetes.

Angiotensin II regulates nephrogenesis and renal vascular development

1995 ◽  
Vol 269 (1) ◽  
pp. F110-F115 ◽  
Author(s):  
A. Tufro-McReddie ◽  
L. M. Romano ◽  
J. M. Harris ◽  
L. Ferder ◽  
R. A. Gomez
Keyword(s):  
Angiotensin Ii ◽  
Kidney Development ◽  
Rana Catesbeiana ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Ang Ii ◽  
Newborn Rats ◽  
Sprague Dawley ◽  
Renal Growth ◽  
Glomerular Size ◽  
Renal Vascular

To test the hypothesis that angiotensin II (ANG II) is necessary for normal embryonic and postnatal kidney development, the effect of angiotensin receptor blockade or angiotensin converting enzyme inhibition on nephrovascular development was studied in newborn Sprague-Dawley rats and in Rana catesbeiana tadpoles undergoing prometamorphosis. Blockade of ANG II type 1 receptor (AT1) in newborn rats induced an arrest in nephrovascular maturation and renal growth, resulting in altered kidney architecture, characterized by fewer, thicker, and shorter afferent arterioles, reduced glomerular size and number, and tubular dilatation. Inhibition of ANG II generation in tadpoles induced even more marked developmental renal abnormalities. Blockade of ANG II type 2 receptor (AT2) in newborn rats did not alter renal growth or morphology. Results indicate that ANG II regulates nephrovascular development, a role that is conserved across species.

scholarly journals Salvianolic Acid B Attenuates Rat Hepatic Fibrosis via Downregulating Angiotensin II Signaling

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Shu Li ◽  
Lina Wang ◽  
Xiuchuan Yan ◽  
Qinglan Wang ◽  
Yanyan Tao ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Hepatic Fibrosis ◽  
Water Soluble ◽  
Salvianolic Acid B ◽  
Type I ◽  
Ang Ii ◽  
Radix Salviae Miltiorrhizae ◽  
Fibrotic Liver ◽  
Salvianolic Acid

The renin-angiotensin system (RAS) plays an important role in hepatic fibrosis. Salvianolic acid B (Sal B), one of the water-soluble components from Radix Salviae miltiorrhizae, has been used to treat hepatic fibrosis, but it is still not clear whether the effect of Sal B is related to angiotensin II (Ang II) signaling pathway. In the present study, we studied Sal B effect on rat liver fibrosis and Ang-II related signaling mediators in dimethylnitrosamine-(DMN-) induced rat fibrotic modelin vivoand Ang-II stimulated hepatic stellate cells (HSCs)in vitro, with perindopril or losartan as control drug, respectively. The results showed that Sal B and perindopril inhibited rat hepatic fibrosis and reduced expression of Ang II receptor type 1 (AT1R) and ERK activation in fibrotic liver. Sal B and losartan also inhibited Ang II-stimulated HSC activation including cell proliferation and expression of type I collagen I (Col-I) andα-smooth muscle actin (α-SMA) productionin vitro, reduced the gene expression of transforming growth factor beta (TGF-β), and downregulated AT1R expression and ERK and c-Jun phosphorylation. In conclusion, our results indicate that Sal B may exert an antihepatic fibrosis effect via downregulating Ang II signaling in HSC activation.

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.

AT2 receptor-mediated vasodilation in the heart: effect of myocardial infarction

2001 ◽  
Vol 281 (6) ◽  
pp. H2590-H2596 ◽  
Author(s):  
Martin P. Schuijt ◽  
Munesh Basdew ◽  
Richard van Veghel ◽  
René de Vries ◽  
Pramod R. Saxena ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Coronary Artery Ligation ◽  
Sham Operation ◽  
Ang Ii ◽  
Artery Ligation ◽  
Systemic Hemodynamic ◽  
Functional Consequences ◽  
Receptor Upregulation ◽  
Renal Vascular

To investigate the functional consequences of postinfarct cardiac angiotensin (ANG) type 2 (AT2) receptor upregulation, rats underwent coronary artery ligation or sham operation and were infused with ANG II 3–4 wk later, when scar formation is complete. ANG II increased mean arterial pressure (MAP) more modestly in infarcted animals than in sham animals. The AT1 receptor antagonist irbesartan, but not the AT2 receptor antagonist PD123319, decreased MAP and antagonized the ANG II-mediated systemic hemodynamic effects. Myocardial (MVC) but not renal vascular conductance (RVC) was diminished in infarcted versus sham rats. ANG II did not affect MVC and reduced RVC in all rats. MVC was unaffected by irbesartan and PD123319 in all animals. However, with PD123319, ANG II reduced MVC in sham but not infarcted animals, and, with irbesartan, ANG II increased MVC in infarcted but not sham animals. Irbesartan increased RVC and antagonized the ANG II-mediated renal effects in all animals. RVC, at baseline or with ANG II, was not affected by PD123319 in infarcted and sham animals. In conclusion, coronary but not renal AT2 receptor stimulation results in vasodilation, and this effect is enhanced in infarcted rats.

scholarly journals Carvedilol Inhibits Angiotensin II-Induced Proliferation and Contraction in Hepatic Stellate Cells through the RhoA/Rho-Kinase Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Ying Wu ◽  
Zhen Li ◽  
Sining Wang ◽  
Aiyuan Xiu ◽  
Chunqing Zhang
Keyword(s):  
Cell Cycle ◽  
Angiotensin Ii ◽  
Liver Fibrosis ◽  
Cell Cycle Progression ◽  
Rho Kinase ◽  
Cell Counting ◽  
Type I ◽  
Dependent Manner ◽  
Ang Ii ◽  
Cycle Progression

Aim. Carvedilol is a nonselective beta-blocker used to reduce portal hypertension. This study investigated the effects and potential mechanisms of carvedilol in angiotensin II- (Ang II-) induced hepatic stellate cell (HSC) proliferation and contraction. Methods. The effect of carvedilol on HSC proliferation was measured by Cell Counting Kit-8 (CCK-8). Cell cycle progression and apoptosis in HSCs were determined by flow cytometry. A collagen gel assay was used to confirm HSC contraction. The extent of liver fibrosis in mice was evaluated by hematoxylin-eosin (H&E) and Sirius Red staining. Western blot analyses were performed to detect the expression of collagen I, collagen III, α-smooth muscle actin (α-SMA), Ang II type I receptor (AT1R), RhoA, Rho-kinase 2 (ROCK2), and others. Results. The results showed that carvedilol inhibited HSC proliferation and arrested the cell cycle at the G0/G1 phase in a dose-dependent manner. Carvedilol also modulated Bcl-2 family proteins and increased apoptosis in Ang II-treated HSCs. Furthermore, carvedilol inhibited HSC contraction induced by Ang II, an effect that was associated with AT1R-mediated RhoA/ROCK2 pathway interference. In addition, carvedilol reduced α-SMA expression and collagen deposition and attenuated liver fibrosis in carbon tetrachloride (CCl4)-treated mice. The in vivo data further confirmed that carvedilol inhibited the expression of angiotensin-converting enzyme (ACE), AT1R, RhoA, and ROCK2. Conclusions. The results indicated that carvedilol dose-dependently inhibited Ang II-induced HSC proliferation by impeding cell cycle progression, thus alleviating hepatic fibrosis. Furthermore, carvedilol could inhibit Ang II-induced HSC contraction by interfering with the AT1R-mediated RhoA/ROCK2 pathway.

scholarly journals Angiotensin II enhances GABAB receptor-mediated responses and expression in nucleus tractus solitarii of rats

2009 ◽  
Vol 297 (5) ◽  
pp. H1837-H1844 ◽  
Author(s):  
Qi Zhang ◽  
Fanrong Yao ◽  
Stephen T. O'Rourke ◽  
Steven Y. Qian ◽  
Chengwen Sun
Keyword(s):  
Angiotensin Ii ◽  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Gabab Receptor ◽  
Receptor Expression ◽  
Nucleus Tractus Solitarii ◽  
Neuronal Cultures ◽  
Ang Ii ◽  
Intracerebroventricular Infusion ◽  
Cgp 35348

Angiotensin II (ANG II) increases GABAB receptor expression in neuronal cultures from the nucleus tractus solitarii (NTS). In the present study, the chronic effects of ANG II on GABAB receptor expression and activity were examined in the NTS of Sprague-Dawley rats. Intracerebroventricular infusion of ANG II caused a significant elevation in blood pressure (BP) and an increase in GABAB receptor expression in the NTS. Conversely, chronic NG-nitro-l-arginine methyl ester (l-NAME) treatment also increased BP, but had no effect on GABAB receptor expression in the NTS. Next, we examined the BP response to the GABAB receptor agonist baclofen microinjected into the NTS of ANG II- or artificial cerebrospinal fluid (aCSF)-infused rats. NTS microinjection of baclofen increased BP in both groups of rats. However, the pressor response to baclofen was enhanced in ANG II-infused rats compared with aCSF-infused rats. In addition, bilateral microinjection of the GABAB receptor antagonist CGP-35348 into the NTS evoked a decrease in BP in both group of rats, and the depressor responses to CGP-35348 were enhanced in the ANG II-infused rats. In contrast, the pressor responses to the GABAA receptor agonist muscimol and the depressor responses to the GABAA receptor antagonist bicuculline were comparable between aCSF- and ANG II-infused rats. These results indicate that chronic ANG II infusion stimulates GABAB receptor expression and augments GABAB receptor-mediated responses in the NTS. This effect could contribute to the central nervous system actions of ANG II that result in dampening of baroreflexes and elevation in arterial BP.

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