scholarly journals The Effects of Central Angiotensin II and Its Specific Blockers on Nociception. Possible Interactions with Oxidative Stress Status / Efekti Centralnog Angiotenzina II I Njegovih Specifičnih Blokatora Na Nocicepciju. Moguće Interakcije Sa Statusom Oksidativnog Stresa

2013 ◽  
Vol 32 (1) ◽  
pp. 52-58 ◽  
Author(s):  
Oana Arcan ◽  
Alin Ciobica ◽  
Walther Bild ◽  
Bogdan Stoica ◽  
Lucian Hritcu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Ii ◽  
Analgesic Effect ◽  
Pain Perception ◽  
Ace Inhibitor ◽  
Renin Angiotensin System ◽  
Latency Time ◽  
Ang Ii ◽  
Hot Plate ◽  
At2 Receptors

SummaryIt has already been demonstrated that a complete brain renin-angiotensin system (RAS) exists distinctly separate from the peripheral system and is implicated in complex functions such as memory, emotional responses and pain. Regarding the implications of angiotensin II (the main bioactive peptide of RAS) in pain, although there are many studies in this area of research, most of the results are controversial. Also, it seems that oxidative stress follows angiotensin II infusion, but the role of AT1 vs. AT2 receptors is not well established. In this context, we were interested in studying the effects of central RAS on nociception, through the intracerebroventricular administration of losartan and PD-123177 (antagonists for the AT1/AT2 receptors), as well as an ACE inhibitor (captopril) and also angiotensin II in rats, which were subsequently tested using the hot-plate task, a well known behavioral test for pain perception. We present here the analgesic effect of angiotensin II administration, as shown by in creased latency-time in the hot-plate, as well as a nociceptive effect of angiotensin II blockers like AT1 and AT2 specific antagonists (losartan and PD-123177) and an ACE inhibitor (captopril), as their administration resulted in decreased latency-time. Moreover, we demonstrated a significant correlation between the results of the nociceptive behavioral task and the levels of some main oxidative stress markers. This provides additional evidence for an analgesic effect of Ang II administration, as well as for a nociceptive effect of Ang II blockers. Moreover, a significant correlation between the nociception and angiotensin II-induced oxidative stress is presented.

scholarly journals Pancreatic angiotensin-converting enzyme 2 improves glycemia in angiotensin II-infused mice

2013 ◽  
Vol 304 (8) ◽  
pp. E874-E884 ◽  
Author(s):  
Kavaljit H. Chhabra ◽  
Huijing Xia ◽  
Kim Brint Pedersen ◽  
Robert C. Speth ◽  
Eric Lazartigues
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Ii ◽  
Cell Function ◽  
Therapeutic Potential ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Β Cell ◽  
Mouse Pancreas ◽  
Β Cell Function ◽  
The Impact

An overactive renin-angiotensin system (RAS) is known to contribute to type 2 diabetes mellitus (T2DM). Although ACE2 overexpression has been shown to be protective against the overactive RAS, a role for pancreatic ACE2, particularly in the islets of Langerhans, in regulating glycemia in response to elevated angiotensin II (Ang II) levels remains to be elucidated. This study examined the role of endogenous pancreatic ACE2 and the impact of elevated Ang II levels on the enzyme's ability to alleviate hyperglycemia in an Ang II infusion mouse model. Male C57bl/6J mice were infused with Ang II or saline for a period of 14 days. On the 7th day of infusion, either an adenovirus encoding human ACE2 (Ad-hACE2) or a control adenovirus (Ad-eGFP) was injected into the mouse pancreas. After an additional 7–8 days, glycemia and plasma insulin levels as well as RAS components expression and oxidative stress were assessed. Ang II-infused mice exhibited hyperglycemia, hyperinsulinemia, and impaired glucose-stimulated insulin secretion from pancreatic islets compared with control mice. This phenotype was associated with decreased ACE2 expression and activity, increased Ang II type 1 receptor (AT1R) expression, and increased oxidative stress in the mouse pancreas. Ad-hACE2 treatment restored pancreatic ACE2 expression and compensatory activity against Ang II-mediated impaired glycemia, thus improving β-cell function. Our data suggest that decreased pancreatic ACE2 is a link between overactive RAS and impaired glycemia in T2DM. Moreover, maintenance of a normal endogenous ACE2 compensatory activity in the pancreas appears critical to avoid β-cell dysfunction, supporting a therapeutic potential for ACE2 in controlling diabetes resulting from an overactive RAS.

scholarly journals Effects of Resveratrol on the Renin-Angiotensin System in the Aging Kidney

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1741 ◽  
Author(s):  
In-Ae Jang ◽  
Eun Kim ◽  
Ji Lim ◽  
Min Kim ◽  
Tae Ban ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Ii ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Renin Angiotensin System ◽  
Organ Damage ◽  
Protective Effects ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Endothelial Nitric Oxide

The renin-angiotensin system (RAS), especially the angiotensin II (Ang II)/angiotensin II type 1 receptor (AT1R) axis, plays an important role in the aging process of the kidney, through increased tissue reactive oxygen species production and progressively increased oxidative stress. In contrast, the angiotensin 1-7 (Ang 1-7)/Mas receptor (MasR) axis, which counteracts the effects of Ang II, is protective for end-organ damage. To evaluate the ability of resveratrol (RSV) to modulate the RAS in aging kidneys, eighteen-month-old male C57BL/6 mice were divided into two groups that received either normal mouse chow or chow containing resveratrol, for six months. Renal expressions of RAS components, as well as pro- and antioxidant enzymes, were measured and mouse kidneys were isolated for histopathology. Resveratrol-treated mice demonstrated better renal function and reduced albuminuria, with improved renal histologic findings. Resveratrol suppressed the Ang II/AT1R axis and enhanced the AT2R/Ang 1-7/MasR axis. Additionally, the expression of nicotinamide adenine dinucleotide phosphate oxidase 4, 8-hydroxy-2′-deoxyguanosine, 3-nitrotyrosine, collagen IV, and fibronectin was decreased, while the expression of endothelial nitric oxide synthase and superoxide dismutase 2 was increased by resveratrol treatment. These findings demonstrate that resveratrol exerts protective effects on aging kidneys by reducing oxidative stress, inflammation, and fibrosis, through Ang II suppression and MasR activation.

scholarly journals Local angiotensin II aggravates cardiac remodeling in hypertension

2010 ◽  
Vol 299 (5) ◽  
pp. H1328-H1338 ◽  
Author(s):  
Jiang Xu ◽  
Oscar A. Carretero ◽  
Tang-Dong Liao ◽  
Hongmei Peng ◽  
Edward G. Shesely ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Transforming Growth Factor ◽  
Renin Angiotensin System ◽  
Transforming Growth Factor Β ◽  
Cardiac Effect ◽  
Ang Ii ◽  
Specific Expression

Angiotensin II (ANG II) contributes to hypertension, cardiac hypertrophy, fibrosis, and dysfunction; however, it is difficult to separate the cardiac effect of ANG II from its hemodynamic action in vivo. To overcome the limitations, we used transgenic mice with cardiac-specific expression of a transgene fusion protein that releases ANG II from cardiomyocytes (Tg-ANG II) and treated them with deoxycorticosterone acetate (DOCA)-salt to suppress their systemic renin-angiotensin system. Using this unique model, we tested the hypothesis that cardiac ANG II, acting on the angiotensin type 1 receptor (AT1R), increases inflammation, oxidative stress, and apoptosis, accelerating cardiac hypertrophy and fibrosis. Male Tg-ANG II mice and their nontransgenic littermates (n-Tg) were uninephrectomized and divided into the following three groups: 1) vehicle-treated normotensive controls; 2) DOCA-salt; and 3) DOCA-salt + valsartan (AT1R blocker).Under basal conditions, systolic blood pressure (SBP) and cardiac phenotypes were similar between strains. In DOCA-salt hypertension, SBP increased similarly in both n-Tg and Tg-ANG II, and cardiac function did not differ between strains; however, Tg-ANG II had 1) greater ventricular hypertrophy as well as interstitial and perivascular fibrosis; 2) a higher number of deoxynucleotidyl-transferase-mediated dUTP nick end labeling-positive cells and infiltrating macrophages; 3) increased protein expression of NADPH oxidase 2 and transforming growth factor-β1; and 4) downregulation of phosphatidylinositol 3-kinase (PI 3-kinase) and protein kinase B (Akt) phosphorylation. Valsartan partially reversed these effects in Tg-ANG II but not in n-Tg. We conclude that, when hemodynamic loading conditions remain unchanged, cardiac ANG II does not alter heart size or cardiac functions. However, in animals with hypertension, cardiac ANG II, acting via AT1R, enhances inflammation, oxidative stress, and cell death (most likely via downregulation of PI 3-kinase and Akt), contributing to cardiac hypertrophy and fibrosis.

scholarly journals AT1 and AT2 receptors modulate renal tubular cell necroptosis in angiotensin II-infused renal injury mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yongjun Zhu ◽  
Hongwang Cui ◽  
Jie Lv ◽  
Haiqin Liang ◽  
Yanping Zheng ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Renal Injury ◽  
Critical Role ◽  
Kidney Injury ◽  
Renin Angiotensin System ◽  
Tubular Cell ◽  
Tubular Damage ◽  
Renal Tubular Cell ◽  
Ang Ii ◽  
Renal Tubular

AbstractAbnormal renin-angiotensin system (RAS) activation plays a critical role in the initiation and progression of chronic kidney disease (CKD) by directly mediating renal tubular cell apoptosis. Our previous study showed that necroptosis may play a more important role than apoptosis in mediating renal tubular cell loss in chronic renal injury rats, but the mechanism involved remains unknown. Here, we investigate whether blocking the angiotensin II type 1 receptor (AT1R) and/or angiotensin II type 2 receptor (AT2R) beneficially alleviates renal tubular cell necroptosis and chronic kidney injury. In an angiotensin II (Ang II)-induced renal injury mouse model, we found that blocking AT1R and AT2R effectively mitigates Ang II-induced increases in necroptotic tubular epithelial cell percentages, necroptosis-related RIP3 and MLKL protein expression, serum creatinine and blood urea nitrogen levels, and tubular damage scores. Furthermore, inhibition of AT1R and AT2R diminishes Ang II-induced necroptosis in HK-2 cells and the AT2 agonist CGP42112A increases the percentage of necroptotic HK-2 cells. In addition, the current study also demonstrates that Losartan and PD123319 effectively mitigated the Ang II-induced increases in Fas and FasL signaling molecule expression. Importantly, disruption of FasL significantly suppressed Ang II-induced increases in necroptotic HK-2 cell percentages, and necroptosis-related proteins. These results suggest that Fas and FasL, as subsequent signaling molecules of AT1R and AT2R, might involve in Ang II-induced necroptosis. Taken together, our results suggest that Ang II-induced necroptosis of renal tubular cell might be involved both AT1R and AT2R and the subsequent expression of Fas, FasL signaling. Thus, AT1R and AT2R might function as critical mediators.

scholarly journals Intracrine angiotensin II functions originate from noncanonical pathways in the human heart

2016 ◽  
Vol 311 (2) ◽  
pp. H404-H414 ◽  
Author(s):  
Carlos M. Ferrario ◽  
Sarfaraz Ahmad ◽  
Jasmina Varagic ◽  
Che Ping Cheng ◽  
Leanne Groban ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Functional Significance ◽  
Vascular Remodeling ◽  
Human Heart ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Extended Form ◽  
Angiotensin I ◽  
Angiotensin System ◽  
Ras Genes

Although it is well-known that excess renin angiotensin system (RAS) activity contributes to the pathophysiology of cardiac and vascular disease, tissue-based expression of RAS genes has given rise to the possibility that intracellularly produced angiotensin II (Ang II) may be a critical contributor to disease processes. An extended form of angiotensin I (Ang I), the dodecapeptide angiotensin-(1–12) [Ang-(1–12)], that generates Ang II directly from chymase, particularly in the human heart, reinforces the possibility that an alternative noncanonical renin independent pathway for Ang II formation may be important in explaining the mechanisms by which the hormone contributes to adverse cardiac and vascular remodeling. This review summarizes the work that has been done in evaluating the functional significance of Ang-(1–12) and how this substrate generated from angiotensinogen by a yet to be identified enzyme enhances knowledge about Ang II pathological actions.

Thermal responses to central angiotensin II, SQ 20881, and dopamine infusions in sheep

1985 ◽  
Vol 248 (3) ◽  
pp. R371-R377 ◽  
Author(s):  
B. S. Huang ◽  
M. J. Kluger ◽  
R. L. Malvin
Keyword(s):  
Angiotensin Ii ◽  
Body Temperature ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Significant Rise ◽  
Ang Ii ◽  
Deep Body Temperature ◽  
Angiotensin System ◽  
Conscious Sheep

The thermoregulatory role of brain angiotensin II (ANG II) was tested by intracerebroventricular (IVT) infusion of ANG II or the converting enzyme inhibitor SQ 20881 (SQ) in 15 conscious sheep. Deep body temperature decreased 0.30 +/- 0.07 degree C (SE) during the 3-h period of IVT ANG II (25 ng/min) infusion (P less than 0.05) and increased 0.50 +/- 0.13 degree C during IVT SQ (1 microgram/min) infusion (P less than 0.01). To determine whether the rise in body temperature after IVT SQ infusion might be the result of a central renin-angiotensin system (RAS), SQ was infused IVT in five conscious sheep 20 h after bilateral nephrectomy. This resulted in a significant rise in body temperature of 0.28 +/- 0.05 degree C (P less than 0.05). When vasopressin antidiuretic hormone (ADH) was infused intravenously at the same time of IVT SQ infusion, the rise in temperature was depressed, but ADH did not lower the temperature below basal. IVT dopamine (20 micrograms/min) increased body temperature by 0.40 +/- 0.04 degree C (P less than 0.01), which was qualitatively similar to the result with IVT SQ. These data support the hypothesis that endogenous brain ANG II may play a role in thermoregulation. Furthermore, plasma ADH level, regulated in part by brain ANG II, is probably not the mediator of that thermoregulation. The similar effects of IVT dopamine and SQ on body temperature strengthen the hypothesis that dopamine may be involved in the central action of brain ANG II.

scholarly journals Preparation and Analysis of New 1,3,5-Trisubstituted-2-Pyrazolines Derivative for Their Analgesic Potential

2021 ◽  
pp. 153-164
Author(s):  
Jitendra Kumar Chaudhary ◽  
Alok Pal Jain ◽  
O. P. Tiwari
Keyword(s):  
Acetic Acid ◽  
Analgesic Effect ◽  
Latency Time ◽  
Hot Plate ◽  
Phenyl Hydrazine ◽  
Hot Plate Test ◽  
Test Technique ◽  
Plate Test ◽  
Withdrawal Latency ◽  
In Series

The goal of the study was to develop, synthesise, and characterise a novel 1,3,5-trisubstituted-2-pyrazolines derivative, as well as to assess its analgesic potential. The reaction of chalcone derivatives with 4-hydrazinylbenzene sulfonamide hydrochloride and phenyl hydrazine hydrochloride yielded 1,3,5-tri-substituted-2-pyrazolines derivatives. The IR, 1HNMR, and mass spectrum analyses were used to characterise a total of sixteen substances. Analgesic activity of the proposed substances has been tested. The analgesic effect of the produced compounds was tested using two methods: the hot plate test technique and acetic acid induced writhing in mice. To compare the effectiveness, pentazocine and acetyl acetic acid were utilised as reference drugs. The hot plate test technique and acetic acid induced writhing in mice were used to assess the analgesic effect of the 16 produced chemical series A1-A8, and B1-B8. The evaluation's outcomes were viewed using Pentazocine and acetyl acetic acid as the standard drugs. In a 90-minute hot plate test, compounds A2 (10.30 s), A4 (9.45 s), A7 (11.65 s), and A8 (11.26 s) showed a delay in paw withdrawal latency time. Compounds B2 (9.10 s) and B7 (10.42 s) prolong the paw withdrawal latency time after 90 minutes in series B1-B8, reduce the pain feeling, and inhibit pain induced by heat methods. Compounds A2, A5, A6, A7, and A8 from Series A1-A8 showed 83.00, 76.01, 80.34, 86.99, 88.15 percent inhibition, substantially (p0.05 and p0.001, respectively), and decreased the number of wriths caused by 0.6 percent acetic acid at a dosage of 10 mg/kg. Acetylsalicylic acid (10 mg/kg) appears to be more successful in lowering the number of wriths, with a 99.0% reduction in the number of wriths (p0.001). B1, B3, and B4 have the least amount of active activity. These all finding suggest that these synthesized compounds have the potential as analgesic agent.

scholarly journals The Biochemical Effects of Angiotensin-(1-7) on the Oxidative Stress Metabolism and Their Specific Parameters from the Temporal Lobe

2020 ◽  
Vol 71 (6) ◽  
pp. 307-311
Author(s):  
Sorin Ungurianu ◽  
Constantin Trus ◽  
Roxana-Rosmary Enciu
Keyword(s):  
Oxidative Stress ◽  
Temporal Lobe ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Angiotensin Peptides ◽  
Vascular Area ◽  
Ang Iv ◽  
The One

It is already known from a variety of previous reports that an independent brain renin�angiotensin system (RAS) exists, completely separated from the one in the periphery. This independent brain RAS has all the precursors and the enzymatic structures necessary for the generation of the angiotensin peptides. Thus, in the last few years various groups started focusing on the more central effects of less known angiotensins (e.g in comparison with Angiotensin (Ang) II), namely Ang III, Ang IV, Ang-(1�7) or Ang 5-8. One of these newly emerging angiotensins which has become an increased center of interest in many studies is Ang-(1-7), which is a heptapeptide previously described especially for its opposite effects to Ang II, in the peripheral vascular area, but also described for some opposite central functions vs. Ang II. These aspects are completed with the fact that it was recently suggested that the renin�angiotensin system could modulate the oxidative stress metabolism, and also it seems that the manifestations of Angiotensin-(1-7) on the basal oxidative stress status are contradictory, with a variety of reports describing controversial (e.g. both pro-oxidant and antioxidant actions) effects for this heptapeptide. Our results presented here are confirming a possible antioxidant effect of Ang-(1�7) administration on rat, as shown by the increased levels of antioxidant enzymes from the temporal lobe (superoxide dismutase and glutathione peroxidase) and decreased levels of malondialdehyde, as an important lipid peroxidation parameter.

Abstract P612: The AA2-Ratio: Towards Improved Screening for Primary Aldosteronism

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Marko Poglitsch ◽  
Ashraf H Ahmed ◽  
Andrea Stoller ◽  
Dunja van Oyen ◽  
Oliver Domenig ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Primary Aldosteronism ◽  
Ace Inhibitor ◽  
False Negative ◽  
Renin Angiotensin System ◽  
Ace Inhibition ◽  
Serum Samples ◽  
Drug Interference ◽  
Salt Loading ◽  
Hypertensive Patients

Background: Primary aldosteronism (PA) is a widely under-diagnosed, potentially curable and specifically treatable cause of hypertension. PA screening involves measuring the aldosterone-to-renin-ratio (ARR), but false negative results can occur in the setting of medications, which block the renin-angiotensin system (RAS). Withdrawing RAS blockers from patients with resistant hypertension is not without cardiovascular risk. A novel diagnostic approach, the aldosterone-to-angiotensin-II-ratio (AA2-Ratio), has the potential for less drug interference and improved reliability in PA screening and confirmation of diagnosis. Methods: Serum samples from 80 patients undergoing PA confirmation testing were analyzed. Sampling was performed in a recumbent (7 a.m.) and in an upright (10 a.m.) position before and after 4 days of oral administration of fludrocortisone and salt loading. The concentrations of renin, aldosterone and equilibrium Angiotensin-II were determined and ARR and AA2-Ratios were calculated. The interference of ACE-inhibition with the AA2-Ratio was investigated in healthy volunteers receiving 10mg enalapril daily for 8 days. Results: Renin concentration was undetectable in more than 40% of samples, while equilibrium Angiotensin-II was measurable in 98% of all 320 samples analyzed. Angiotensin-II levels were significantly higher in upright collected samples compared to samples collected in a recumbent position. Comparison of the ARR with the AA2-Ratio revealed a significantly larger diagnostic window for the AA2-Ratio. While the ARR was significantly suppressed by ACE-inhibitor treatment, the AA2-Ratio remained unaffected by ACE-inhibition. Conclusion: The AA2-Ratio may be superior to the ARR in PA screening among hypertensive patients. Equilibrium Angiotensin-II levels show expected responses to posture and appear to outperform renin concentration as a marker for RAS activation in terms of sensitivity, giving a measurable readout even in clinical states characterized by markedly suppressed RAS activity. The stability of the AA2-Ratio in the presence of ACE-inhibition points to a potential use of the AA2-Ratio PA screening in hypertensive patients without ACE-inhibitor discontinuation.

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