Angiotensin II Type 1 receptor induced signal-transduction pathways as new targets for pharmacological treatment of the renin-angiotensin system

1996 ◽  
Vol 91 (S1) ◽  
pp. 91-96 ◽  
Author(s):  
W. Schorb ◽  
G. Ertl
Keyword(s):  
Signal Transduction ◽  
Angiotensin Ii ◽  
Pharmacological Treatment ◽  
Renin Angiotensin System ◽  
Signal Transduction Pathways ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
New Targets ◽  
Induced Signal

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 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.

scholarly journals AT1 Receptor Gene Polymorphisms in relation to Postprandial Lipemia

2012 ◽  
Vol 2012 ◽  
pp. 1-6
Author(s):  
B. Klop ◽  
T. M. van den Berg ◽  
A. P. Rietveld ◽  
J. Chaves ◽  
J. T. Real ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Gene Polymorphisms ◽  
Receptor Gene ◽  
Postprandial Lipemia ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
The Common ◽  
Receptor Gene Polymorphisms

Background. Recent data suggest that the renin-angiotensin system may be involved in triglyceride (TG) metabolism. We explored the effect of the common A1166C and C573T polymorphisms of the angiotensin II type 1 receptor (AT1R) gene on postprandial lipemia.Methods. Eighty-two subjects measured daytime capillary TG, and postprandial lipemia was estimated as incremental area under the TG curve. The C573T and A1166C polymorphisms of the AT1R gene were determined.Results. Postprandial lipemia was significantly higher in homozygous carriers of the 1166-C allele (9.39±8.36 mM*h/L) compared to homozygous carriers of the 1166-A allele (2.02±6.20 mM*h/L) (P<0.05). Postprandial lipemia was similar for the different C573T polymorphisms.Conclusion. The 1166-C allele of the AT1R gene seems to be associated with increased postprandial lipemia. These data confirm the earlier described relationships between the renin-angiotensin axis and triglyceride metabolism.

scholarly journals Cardiac hypertrophy in mice submitted to a swimming protocol: influence of training volume and intensity on myocardial renin-angiotensin system

2019 ◽  
Vol 316 (6) ◽  
pp. R776-R782 ◽  
Author(s):  
Douglas dos Santos Soares ◽  
Graziela Hünning Pinto ◽  
Amanda Lopes ◽  
Daniel Sturza Lucas Caetano ◽  
Thaiane Gomes Nascimento ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Renin Angiotensin System ◽  
Oxidative Capacity ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Angiotensin Peptides ◽  
Physiological Cardiac Hypertrophy ◽  
Pathological Hypertrophy

Exercise promotes physiological cardiac hypertrophy and activates the renin-angiotensin system (RAS), which plays an important role in cardiac physiology, both through the classical axis [angiotensin II type 1 receptor (AT1R) activated by angiotensin II (ANG II)] and the alternative axis [proto-oncogene Mas receptor (MASR) activated by angiotensin-(1–7)]. However, very intense exercise could have deleterious effects on the cardiovascular system. We aimed to analyze the cardiac hypertrophy phenotype and the classical and alternative RAS axes in the myocardium of mice submitted to swimming exercises of varying volume and intensity for the development of cardiac hypertrophy. Male Balb/c mice were divided into three groups, sedentary, swimming twice a day without overload (T2), and swimming three times a day with a 2% body weight overload (T3), totaling 6 wk of training. Both training groups developed similar cardiac hypertrophy, but only T3 mice improved their oxidative capacity. We observed that T2 had increased levels of MASR, which was followed by the activation of its main downstream protein AKT; meanwhile, AT1R and its main downstream protein ERK remained unchanged. Furthermore, no change was observed regarding the levels of angiotensin peptides, in either group. In addition, we observed no change in the ratio of expression of the myosin heavy chain β-isoform to that of the α-isoform. Fibrosis was not observed in any of the groups. In conclusion, our results suggest that increasing exercise volume and intensity did not induce a pathological hypertrophy phenotype, but instead improved the oxidative capacity, and this process might have the participation of the RAS alternative axis.

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