scholarly journals Antihypertensive and cardiovascular effects of combined blockade of renin-angiotensin system with ACE inhibitor and angiotensin II type 1 receptor blocker in hypertensive patients: A 24-week randomized controlled double-dummy trial

2006 ◽  
Vol 2 (1) ◽  
Author(s):  
Christiano Argano ◽  
Rosario Scaglione ◽  
Tiziana Di Chiara ◽  
Daniela Colomba ◽  
Gaspare Parrinello ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Ace Inhibitor ◽  
Renin Angiotensin System ◽  
Cardiovascular Effects ◽  
Receptor Blocker ◽  
Angiotensin System ◽  
Hypertensive Patients ◽  
Renin Angiotensin ◽  
Randomized Controlled

scholarly journals Renin-Angiotensin System Blockers and the COVID-19 Pandemic

Hypertension ◽  
2020 ◽  
Vol 75 (6) ◽  
pp. 1382-1385 ◽  
Author(s):  
A.H. Jan Danser ◽  
Murray Epstein ◽  
Daniel Batlle
Keyword(s):  
Angiotensin Ii ◽  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Receptor Blockers ◽  
Renin Angiotensin System Blockers

During the spread of the severe acute respiratory syndrome coronavirus-2, some reports of data still emerging and in need of full analysis indicate that certain groups of patients are at risk of COVID-19. This includes patients with hypertension, heart disease, diabetes mellitus, and clearly the elderly. Many of those patients are treated with renin-angiotensin system blockers. Because the ACE2 (angiotensin-converting enzyme 2) protein is the receptor that facilitates coronavirus entry into cells, the notion has been popularized that treatment with renin-angiotensin system blockers might increase the risk of developing a severe and fatal severe acute respiratory syndrome coronavirus-2 infection. The present article discusses this concept. ACE2 in its full-length form is a membrane-bound enzyme, whereas its shorter (soluble) form circulates in blood at very low levels. As a mono-carboxypeptidase, ACE2 contributes to the degradation of several substrates including angiotensins I and II. ACE (angiotensin-converting enzyme) inhibitors do not inhibit ACE2 because ACE and ACE2 are different enzymes. Although angiotensin II type 1 receptor blockers have been shown to upregulate ACE2 in experimental animals, the evidence is not always consistent and differs among the diverse angiotensin II type 1 receptor blockers and differing organs. Moreover, there are no data to support the notion that ACE inhibitor or angiotensin II type 1 receptor blocker administration facilitates coronavirus entry by increasing ACE2 expression in either animals or humans. Indeed, animal data support elevated ACE2 expression as conferring potential protective pulmonary and cardiovascular effects. In summary, based on the currently available evidence, treatment with renin-angiotensin system blockers should not be discontinued because of concerns with coronavirus infection.

scholarly journals Effect of Sensor-Augmented Pump Treatment Versus Multiple Daily Injections on Albuminuria: A 1-Year Randomized Study

2015 ◽  
Vol 100 (11) ◽  
pp. 4181-4188 ◽  
Author(s):  
Signe Rosenlund ◽  
Tine Willum Hansen ◽  
Peter Rossing ◽  
Steen Andersen
Keyword(s):  
Type 1 Diabetes ◽  
Renin Angiotensin System ◽  
Glucose Variability ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Randomized Controlled ◽  
Multiple Daily Injections ◽  
51Cr Edta ◽  
History Of

Context: The effect of glycemic control on persisting albuminuria remains unclear. Insulin delivery and glucose variability may be important. Objective: This study aimed to investigate the effect of 1-year treatment with sensor-augmented insulin pump (SAP) or multiple daily injections (MDIs) on albuminuria. Design, Patients, and Methods: This was a randomized controlled open-label parallel trial composed of 60 patients with type 1 diabetes with a history of albuminuria and on stable renin-angiotensin system inhibition, were randomly assigned to SAP or MDI. Urine albumin creatinine ratio (UACR) was measured in three urine samples at all visits. Glucose variability and glomerular filtration rate (51Cr-EDTA-GFR) were measured at beginning and study end. Using linear mixed model, change in UACR between groups was analyzed as intention to treat. Main Outcome Measure: Change in UACR was measured. Results: Fifty-five patients (SAP, n = 26; MDI, n = 29) completed the study. Diabetes duration (mean ± SD, 33 ± 12 y), UACR (geometric mean, 99 mg/g; interquartile range, 37–233 mg/g), 51Cr-EDTA-GFR (94 ± 22 mL/min/1.73m2), glycosylated hemoglobin (HbA1c) (9.0 ± 1.1%), glucose variability (calculated as SD), 4.0 ± 1.0 mmol/l; no-group differences (P ≥ .06 for all). After 1 year, change in UACR was mean, −13%; 95% confidence interval, −39 to 22 with SAP vs mean, 30%; 95% CI, −12 to 92% on MDI treatment (unadjusted P = .051; adjusted for HbA1c, P = .04). HbA1c decreased 1.3 ± 1.0 vs 0.6 ± 1.0% (P = .013), glucose variability decreased 0.9 ± 1.1 vs 0.3 ± 1.0 mmol/L (P = .04), and 51Cr-EDTA-GFR declined 5.6 ± 9.6 vs 3.4 ± 13 mL/min/1.73m2 (P = .50) with SAP vs MDI treatment. There were no changes in blood pressure (P ≥ .27). Conclusion: SAP treatment reduced UACR in a randomized controlled trial in type 1 diabetes patients with a history of albuminuria on stable renin-angiotensin system inhibition. Significance was reached after adjustment. SAP treatment reduced HbA1c and glucose variability (calculated as SD).

scholarly journals Inhibition of Endocytosis of Clathrin-Mediated Angiotensin II Receptor Type 1 in Podocytes Augments Glomerular Injury

2019 ◽  
Vol 30 (12) ◽  
pp. 2307-2320 ◽  
Author(s):  
Kazunori Inoue ◽  
Xuefei Tian ◽  
Heino Velazquez ◽  
Keita Soda ◽  
Zhen Wang ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Knockout Mice ◽  
Renin Angiotensin System ◽  
Membrane Dynamics ◽  
Receptor Type ◽  
Angiotensin Ii Receptor ◽  
Double Knockout ◽  
Angiotensin System ◽  
Renin Angiotensin

BackgroundInhibition of the renin-angiotensin system remains a cornerstone in reducing proteinuria and progression of kidney failure, effects believed to be the result of reduction in BP and glomerular hyperfiltration. However, studies have yielded conflicting results on whether podocyte-specific angiotensin II (AngII) signaling directly induces podocyte injury. Previous research has found that after AngII stimulation, β-arrestin–bound angiotensin II receptor type 1 (AT1R) is internalized in a clathrin- and dynamin-dependent manner, and that Dynamin1 and Dynamin2 double-knockout mice exhibit impaired clathrin-mediated endocytosis.MethodsWe used podocyte-specific Dyn double-knockout mice to examine AngII-stimulated AT1R internalization and signaling in primary podocytes and controls. We also examined the in vivo effect of AngII in these double-knockout mice through renin-angiotensin system blockers and through deletion of Agtr1a (which encodes the predominant AT1R isoform expressed in kidney, AT1aR). We tested calcium influx, Rac1 activation, and lamellipodial extension in control and primary podocytes of Dnm double-knockout mice treated with AngII.ResultsWe confirmed augmented AngII-stimulated AT1R signaling in primary Dnm double-knockout podocytes resulting from arrest of clathrin-coated pit turnover. Genetic ablation of podocyte Agtr1a in Dnm double-knockout mice demonstrated improved albuminuria and kidney function compared with the double-knockout mice. Isolation of podocytes from Dnm double-knockout mice revealed abnormal membrane dynamics, with increased Rac1 activation and lamellipodial extension, which was attenuated in Dnm double-knockout podocytes lacking AT1aR.ConclusionsOur results indicate that inhibiting aberrant podocyte-associated AT1aR signaling pathways has a protective effect in maintaining the integrity of the glomerular filtration barrier.

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