The Effects of Renin–angiotensin System Inhibition on Regression of Encapsulating Peritoneal Sclerosis

2008 ◽  
Vol 28 (5_suppl) ◽  
pp. 38-42 ◽  
Author(s):  
Devrim Bozkurt ◽  
Pinar Cetin ◽  
Savas Sipahi ◽  
Ender Hur ◽  
Hasim Nar ◽  
...  
Keyword(s):  
Morphological Changes ◽  
Angiotensin Receptor Blockers ◽  
Isotonic Saline ◽  
Renin Angiotensin System ◽  
Parietal Peritoneum ◽  
Control Group ◽  
Peritoneal Fibrosis ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Beneficial Effects

Background Encapsulating peritoneal sclerosis (EPS) is a clinical syndrome associated with symptoms of ileus and irreversible sclerosis of both visceral and parietal peritoneum. Peritoneal dialysis (PD) patients rarely develop EPS, a severe life-threatening condition of unknown pathogenesis. Angiotensin II is known to promote fibrosis and inflammation in various tissues. Renin–angiotensin system (RAS) blockade provides advantages in the course of diseases such as hypertension, chronic kidney disease, and proteinuria. We have also previously shown that RAS blockade has beneficial effects on hypertonic (3.86%) PD solution-induced peritoneal alterations. Because it shares the same characteristics as other fibrotic processes, peritoneal fibrosis can benefit from RAS blockade. Objective To determine the advantages of RAS blockade in regression of EPS. Methods We divided 56 nonuremic albino Wistar rats into 6 groups: control group ( n = 10), daily intraperitoneal (IP) injection of 2 mL isotonic saline for 3 weeks; CG group ( n = 10), daily IP injection of 2 mL/200 g chlorhexidine gluconate (CG) for 3 weeks; resting group ( n = 10), daily IP injection of CG (0 – 3 weeks) plus peritoneal rest (4 – 6 weeks). After 3 weeks of being injected with CG (0 – 3 weeks), a fourth group ( n = 9) was treated with 100 mg/L enalapril (ENA group); a fifth group ( n = 10) was treated with 80 mg/L valsartan (VAL group), and a sixth group ( n = 7) was treated with 100 mg/L enalapril + 80 mg/L valsartan (ENA+VAL group) in drinking water for an additional 3 weeks (4 – 6 weeks). At the end, a 1-hour peritoneal equilibration test was performed with 25 mL 3.86% PD solution. Dialysate-to-plasma ratio of urea (D/P urea), dialysate WBC count, ultrafiltration volume (UF), and morphological changes of parietal peritoneum were examined. Results Exposure to CG for 3 weeks resulted in alterations in peritoneal transport (increased D/P urea, decreased UF volume; p < 0.05) and morphology (increased inflammation, neovascularization, fibrosis, and peritoneal thickness; p < 0.05). Peritoneal rest had some beneficial effect only on UF failure and dialysate cell count ( p < 0.05). However, RAS blockade was more effective than peritoneal rest with respect to UF volume, vascularity ( p < 0.05), and peritoneal thickness ( p > 0.05). Dual blockade of RAS had no additional beneficial effects. Conclusion We suggest that RAS blockade either with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers may be a more effective option than resting in the management of EPS.

Renin-Angiotensin System and Alzheimer’s Disease Pathophysiology: From the Potential Interactions to Therapeutic Perspectives

2020 ◽  
Vol 27 (6) ◽  
pp. 484-511 ◽  
Author(s):  
Victor Teatini Ribeiro ◽  
Leonardo Cruz de Souza ◽  
Ana Cristina Simões e Silva
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Enzyme Inhibitors ◽  
Angiotensin Receptor Blockers ◽  
Renin Angiotensin System ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Converting Enzyme Inhibitors ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Beneficial Effects

New roles of the Renin-Angiotensin System (RAS), apart from fluid homeostasis and Blood Pressure (BP) regulation, are being progressively unveiled, since the discoveries of RAS alternative axes and local RAS in different tissues, including the brain. Brain RAS is reported to interact with pathophysiological mechanisms of many neurological and psychiatric diseases, including Alzheimer’s Disease (AD). Even though AD is the most common cause of dementia worldwide, its pathophysiology is far from elucidated. Currently, no treatment can halt the disease course. Successive failures of amyloid-targeting drugs have challenged the amyloid hypothesis and increased the interest in the inflammatory and vascular aspects of AD. RAS compounds, both centrally and peripherally, potentially interact with neuroinflammation and cerebrovascular regulation. This narrative review discusses the AD pathophysiology and its possible interaction with RAS, looking forward to potential therapeutic approaches. RAS molecules affect BP, cerebral blood flow, neuroinflammation, and oxidative stress. Angiotensin (Ang) II, via angiotensin type 1 receptors may promote brain tissue damage, while Ang-(1-7) seems to elicit neuroprotection. Several studies dosed RAS molecules in AD patients&#039; biological material, with heterogeneous results. The link between AD and clinical conditions related to classical RAS axis overactivation (hypertension, heart failure, and chronic kidney disease) supports the hypothesized role of this system in AD. Additionally, RAStargeting drugs as Angiotensin Converting Enzyme inhibitors (ACEis) and Angiotensin Receptor Blockers (ARBs) seem to exert beneficial effects on AD. Results of randomized controlled trials testing ACEi or ARBs in AD are awaited to elucidate whether AD-RAS interaction has implications on AD therapeutics.

scholarly journals Functional expression of the renin-angiotensin system in human podocytes

2006 ◽  
Vol 290 (3) ◽  
pp. F710-F719 ◽  
Author(s):  
Max C. Liebau ◽  
D. Lang ◽  
J. Böhm ◽  
N. Endlich ◽  
Martin J. Bek ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Functional Expression ◽  
Kidney Cortex ◽  
Receptor Subtypes ◽  
Ang Ii ◽  
Angiotensin Receptor ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Beneficial Effects ◽  
Glomerular Proteinuria

Experimental and clinical studies impressively demonstrate that angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) significantly reduce proteinuria and retard progression of glomerular disease. The underlying intraglomerular mechanisms are not yet fully elucidated. As podocyte injury constitutes a critical step in the pathogenesis of glomerular proteinuria, beneficial effects of ACEI and ARB may partially result from interference with a local renin-angiotensin system (RAS) in podocytes. The knowledge of expression and function of a local RAS in podocytes is limited. In this study, we demonstrate functional expression of key components of the RAS in differentiated human podocytes: podocytes express mRNA for angiotensinogen, renin, ACE type 1, and the AT1 and AT2 angiotensin receptor subtypes. In Western blot experiments and immunostainings, expression of the AT1 and AT2 receptor was demonstrated both in differentiated human podocytes and in human kidney cortex. ANG II induced a concentration-dependent increase in cytosolic Ca2+ concentration via AT1 receptors in differentiated human podocytes, whereas it did not increase cAMP. Furthermore, ANG II secretion was detected, which was blocked by neither the ACEI captopril nor the renin inhibitor remikiren nor the chymase inhibitor chymostatin. ANG II secretion of podocytes was not increased by mechanical stress. Finally, ANG II was found to increase staurosporine-induced apoptosis in podocytes. We speculate that ACEI and ARB exert their beneficial effects, in part, by interfering with a local RAS in podocytes. Further experiments are required to identify the underlying molecular mechanism(s) of podocyte protection.

HFrEF pharmacological treatment: ACEIs and/or ARBs

ESC CardioMed ◽  
2018 ◽  
pp. 1844-1848
Author(s):  
Marc A. Pfeffer
Keyword(s):  
Heart Failure ◽  
Angiotensin Receptor Blockers ◽  
Antihypertensive Agents ◽  
Drug Effects ◽  
Renin Angiotensin System ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Converting Enzyme Inhibitors ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Reduced Ejection Fraction

Several classes of inhibitors of the renin–angiotensin system were developed as antihypertensive agents. Following the early observations of favourable haemodynamic effects of angiotensin-converting enzyme inhibitors (ACEIs) in patients with congestive heart failure, a series of major randomized outcome trials demonstrated morbidity and mortality benefits of these agents across the spectrum of patients with heart failure with reduced ejection fraction (HFrEF). Angiotensin receptor blockers (ARBs) were then also shown to have similar benefits with a suggestion of some incremental improvements when used together. However, in the trials that randomized patients to a proven dose of an ACEI plus either placebo or an ARB, the combination of the two inhibitors of the renin–angiotensin system resulted in more adverse drug effects without a meaningful improvement in clinical outcomes. This chapter reviews the fundamental underpinnings for use of either an ACEI or ARB to improve prognosis of patients with HFrEF.

Role of the Renin–angiotensin System in the Pathogenesis of Peritoneal Fibrosis

2008 ◽  
Vol 28 (3_suppl) ◽  
pp. 83-87
Author(s):  
Hidetomo Nakamoto ◽  
Hiroe Imai ◽  
Rie Fukushima ◽  
Yuji Ishida ◽  
Yasuhiro Yamanouchi ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Oral Administration ◽  
Renin Angiotensin System ◽  
Peritoneal Fibrosis ◽  
Peritoneal Adhesions ◽  
Angiotensin System ◽  
Daily Group ◽  
Renin Angiotensin ◽  
Group I ◽  
Dialysis Solution

⋄ Background Although the effects of angiotensin type 1 receptor blocker (ARB) have been studied, little is known about ARBs in hypertensive patients undergoing dialysis. In the present study, we evaluated the effect of an ARB, olmesartan medoxomil (CS866), on the progression of peritoneal fibrosis in peritoneal dialysis by examining its effect in a model of peritoneal fibrosis in hypertensive rats. ⋄ Materials and Methods W e all ocated 40 male Wistar rats with 2-kidney, 1-clip renovascular hypertension (2K1C-RVH) to 4 groups (each n = 10) that were dialyzed using various solutions for 42 days as follows: • Group I—10 mL pH 3.5 dialysis solution containing 1.35% glucose • Group II—10 mL pH 3.5 dialysis solution, plus oral administration of CS866 5 mg/kg daily • Group III—10 mL pH 3.5 dialysis solution, plus oral administration of the calcium channel blocker (CCB) amlodipine 3 mg/kg daily • Group IV—10 mL pH 7.0 dialysis solution Dialysis solution was injected every day for 42 days. ⋄ Results Treatment with CS866 and amlodipine induced a significant reduction of blood pressure in 2K1C-RVH rats. In rats treated with pH 3.5 dialysis solution, necropsy findings revealed features identical to those of encapsulating peritoneal sclerosis (EPS). The typical appearance was multiple surfaces covered with granulation tissue or fibrosic tissue or both. Multiple adhesions were present. Microscopic findings revealed that acidic dialysis solution induced peritoneal fibrosis and loss of mesothelium. Treatment with CS866 prevented the progression of peritoneal fibrosis and adhesions. However amlodipine did not improve the progression of peritoneal fibrosis and peritoneal adhesions. In CS866-treated rats, no signs of EPS were present. ⋄ Conclusions Long-term intraperitoneal exposure to acidic dialysis solution produced features typical of EPS. Acidic dialysis solution induces activation of the peritoneal renin– angiotensin system and progression of peritoneal fibrosis. For the peritoneum undergoing peritoneal dialysis, ARB protects against progression of peritoneal fibrosis and peritoneal adhesions.

The Effects of Colchicine on the Progression and Regression of Encapsulating Peritoneal Sclerosis

2008 ◽  
Vol 28 (5_suppl) ◽  
pp. 53-57 ◽  
Author(s):  
Devrim Bozkurt ◽  
Selahattin Bicak ◽  
Savas Sipahi ◽  
Huseyin Taskin ◽  
Ender Hur ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Morphological Changes ◽  
Membrane Integrity ◽  
Isotonic Saline ◽  
Control Group ◽  
Beneficial Effects ◽  
Compact Zone ◽  
Anti Inflammatory ◽  
Group 2 ◽  
Wbc Count

Background Encapsulating peritoneal sclerosis (EPS) is an infrequent but extremely serious complication of long-term peritoneal dialysis. Fibrosis of the submesothelial compact zone and neoangiogenesis underlie the pathophysiology of EPS. Colchicine is a well-known anti-inflammatory and antifibrotic agent that has been used for some fibrosing clinical states, such as liver fibrosis. Objective To determine the antifibrotic and anti-inflammatory effects of colchicine in an EPS rat model in both progression (P) and regression (R). Methods 48 nonuremic albino Wistar rats were divided into 5 groups: control group, 2 mL isotonic saline intraperitoneally (IP) daily for 3 weeks; CG group, IP injection of 2 mL/200 g chlorhexidine gluconate (CG) (0.1%) and ethanol (15%) dissolved in saline, daily for 3 weeks; resting group, CG (0 – 3 weeks) + peritoneal resting (4 – 6 weeks); C-R group, CG (0 – 3 weeks) + 1 mg/L colchicine (4 – 6 weeks); C-P group, CG (0 – 3 weeks) + 1 mg/L colchicine in drinking water (0 – 3 weeks). At the end, a 1-hour peritoneal equilibration test was performed with 25 mL 3.86% peritoneal dialysis solution. Dialysate-to-plasma ratio of urea (D/P urea), dialysate WBC count, ultrafiltration volume, and morphological changes of parietal peritoneum were examined. Result Exposure to CG for 3 weeks resulted in alterations in peritoneal transport (increased D/P urea, decreased ultrafiltration volume; p < 0.05) and morphology (increased inflammation, neovascularization, fibrosis, and peritoneal thickness; p < 0.05). Resting had some beneficial effects on peritoneal derangements; however, once the peritoneum had been stimulated, resting alone was not enough to reverse these pathological changes. Colchicine had more pronounced effects on membrane integrity via decreased inflammation, cell infiltration, and vascularity compared to the resting group. Conclusion We suggest that colchicine may have therapeutic value in the management of EPS.

Imbalance of the renin–angiotensin system may contribute to inflammation and fibrosis in IBD: a novel therapeutic target?

Gut ◽  
2019 ◽  
Vol 69 (5) ◽  
pp. 841-851 ◽  
Author(s):  
Mayur Garg ◽  
Simon G Royce ◽  
Chris Tikellis ◽  
Claire Shallue ◽  
Duygu Batu ◽  
...  
Keyword(s):  
Ace Inhibitors ◽  
Intestinal Inflammation ◽  
Angiotensin Receptor Blockers ◽  
Renin Angiotensin System ◽  
Dependent Manner ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Disease Outcomes ◽  
Collagen Secretion

ObjectiveWe evaluated the influence of the renin–angiotensin system (RAS) on intestinal inflammation and fibrosis.DesignCultured human colonic myofibroblast proliferation and collagen secretion were assessed following treatment with angiotensin (Ang) II and Ang (1–7), their receptor antagonists candesartan and A779, and the ACE inhibitor captopril. Circulating and intestinal RAS components were evaluated in patients with and without IBD. Disease outcomes in patients with IBD treated with ACE inhibitors and angiotensin receptor blockers (ARBs) were assessed in retrospective studies.ResultsHuman colonic myofibroblast proliferation was reduced by Ang (1–7) in a dose-dependent manner (p<0.05). Ang II marginally but not significantly increased proliferation, an effect reversed by candesartan (p<0.001). Colonic myofibroblast collagen secretion was reduced by Ang (1–7) (p<0.05) and captopril (p<0.001), and was increased by Ang II (p<0.001). Patients with IBD had higher circulating renin (mean 25.4 vs 18.6 mIU/L, p=0.026) and ACE2:ACE ratio (mean 0.92 vs 0.69, p=0.015) than controls without IBD. RAS gene transcripts and peptides were identified in healthy and diseased bowels. Colonic mucosal Masson’s trichrome staining correlated with Ang II (r=0.346, p=0.010) and inversely with ACE2 activity (r=−0.373, p=0.006). Patients with IBD who required surgery (1/37 vs 12/75, p=0.034) and hospitalisation (0/34 vs 8/68, p=0.049) over 2 years were less often treated with ACE inhibitors and ARBs than patients not requiring surgery or hospitalisation.ConclusionsThe RAS mediates fibrosis in human cell cultures, is expressed in the intestine and perturbed in intestinal inflammation, and agents targeting this system are associated with improved disease outcomes.

scholarly journals Coronavirus disease 2019 (COVID-19) and the renin-angiotensin system: A closer look at angiotensin-converting enzyme 2 (ACE2)

2020 ◽  
Vol 57 (5) ◽  
pp. 339-350 ◽  
Author(s):  
Annalise E Zemlin ◽  
Owen J Wiese
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Angiotensin Receptor Blockers ◽  
Renin Angiotensin System ◽  
World Health ◽  
Atypical Pneumonia ◽  
Converting Enzyme ◽  
Wholesale Market ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin

Since the first cases of atypical pneumonia linked to the Huanan Seafood Wholesale Market in Wuhan, China, were described in late December 2019, the global landscape has changed radically. In March 2020, the World Health Organization declared COVID-19 a global pandemic, and at the time of writing this review, just over three million individuals have been infected with more than 200,000 deaths globally. Numerous countries are in ‘lockdown’, social distancing is the new norm, even the most advanced healthcare systems are under pressure, and a global economic recession seems inevitable. A novel coronavirus (SARS-CoV-2) was identified as the aetiological agent. From experience with previous coronavirus epidemics, namely the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) in 2004 and 2012 respectively, it was postulated that the angiotensin-converting enzyme-2 (ACE2) receptor is a possible port of cell entry. ACE2 is part of the renin-angiotensin system and is also associated with lung and cardiovascular disorders and inflammation. Recent studies have confirmed that ACE2 is the port of entry for SARS-CoV-2. Male sex, advanced age and a number of associated comorbidities have been identified as risk factors for infection with COVID-19. Many high-risk COVID-19 patients with comorbidities are on ACE inhibitors and angiotensin receptor blockers, and this has sparked debate about whether to continue these treatment regimes. Attention has also shifted to ACE2 being a target for future therapies or vaccines against COVID-19. In this review, we discuss COVID-19 and its complex relationship with ACE2.

Splanchnic blood flow and hepatic glucose production in exercising humans: role of renin-angiotensin system

2001 ◽  
Vol 281 (6) ◽  
pp. R1854-R1861 ◽  
Author(s):  
Raynald Bergeron ◽  
Michael Kjær ◽  
Lene Simonsen ◽  
Jens Bülow ◽  
Dorthe Skovgaard ◽  
...  
Keyword(s):  
Blood Flow ◽  
Renin Angiotensin System ◽  
Glucose Production ◽  
Splanchnic Blood Flow ◽  
Control Group ◽  
Moderate Exercise ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin

The study examined the implication of the renin-angiotensin system (RAS) in regulation of splanchnic blood flow and glucose production in exercising humans. Subjects cycled for 40 min at 50% maximal O2 consumption (V˙o 2 max) followed by 30 min at 70% V˙o 2 maxeither with [angiotensin-converting enzyme (ACE) blockade] or without (control) administration of the ACE inhibitor enalapril (10 mg iv). Splanchnic blood flow was estimated by indocyanine green, and splanchnic substrate exchange was determined by the arteriohepatic venous difference. Exercise led to an ∼20-fold increase ( P < 0.001) in ANG II levels in the control group (5.4 ± 1.0 to 102.0 ± 25.1 pg/ml), whereas this response was blunted during ACE blockade (8.1 ± 1.2 to 13.2 ± 2.4 pg/ml) and in response to an orthostatic challenge performed postexercise. Apart from lactate and cortisol, which were higher in the ACE-blockade group vs. the control group, hormones, metabolites, V˙o 2, and RER followed the same pattern of changes in ACE-blockade and control groups during exercise. Splanchnic blood flow (at rest: 1.67 ± 0.12, ACE blockade; 1.59 ± 0.18 l/min, control) decreased during moderate exercise (0.78 ± 0.07, ACE blockade; 0.74 ± 0.14 l/min, control), whereas splanchnic glucose production (at rest: 0.50 ± 0.06, ACE blockade; 0.68 ± 0.10 mmol/min, control) increased during moderate exercise (1.97 ± 0.29, ACE blockade; 1.91 ± 0.41 mmol/min, control). Refuting a major role of the RAS for these responses, no differences in the pattern of change of splanchnic blood flow and splanchnic glucose production were observed during ACE blockade compared with controls. This study demonstrates that the normal increase in ANG II levels observed during prolonged exercise in humans does not play a major role in the regulation of splanchnic blood flow and glucose production.

Sign in / Sign up

Export Citation Format

Share Document