scholarly journals High-fat diet amplifies renal renin angiotensin system expression, blood pressure elevation, and renal dysfunction caused by Ceacam1 null deletion

2015 ◽  
Vol 309 (9) ◽  
pp. E802-E810 ◽  
Author(s):  
Caixia Li ◽  
Silas A. Culver ◽  
Syed Quadri ◽  
Kelly L. Ledford ◽  
Qusai Y. Al-Share ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
High Fat Diet ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
High Fat ◽  
Angiotensin System ◽  
Collagen Iii ◽  
Renal Expression

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAMl), a substrate of the insulin receptor tyrosine kinase, regulates insulin action by promoting insulin clearance. Global null mutation of Ceacam1 gene ( Cc1−/−) results in features of the metabolic syndrome, including insulin resistance, hyperinsulinemia, visceral adiposity, elevated blood pressure, and albuminuria. It also causes activation of the renal renin-angiotensin system (RAS). In the current study, we tested the hypothesis that high-fat diet enhances the expression of RAS components. Three-month-old wild-type ( Cc1+/+) and Cc1−/− mice were fed either a regular or a high-fat diet for 8 wk. At baseline under regular feeding conditions, Cc1−/− mice exhibited higher blood pressure, urine albumin-to-creatinine ratio (UACR), and renal expression of angiotensinogen, renin/prorenin, angiotensin-converting enzyme, (pro)renin receptor, angiotensin subtype AT1 receptor, angiotensin II, and elevated PI3K phosphorylation, as detected by p85α (Tyr508) immunostaining, inflammatory response, and the expression of collagen I and collagen III. In Cc1+/+ mice, high-fat diet increased blood pressure, UACR, the expression of angiotensin-converting enzyme and angiotensin II, PI3K phosphorylation, inflammatory response, and the expression of collagen I and collagen III. In Cc1−/− mice, high-fat intake further amplified these parameters. Immunohistochemical staining showed increased p-PI3K p85α (Tyr508) expression in renal glomeruli, proximal, distal, and collecting tubules of Cc1−/− mice fed a high-fat diet. Together, this demonstrates that high-fat diet amplifies the permissive effect of Ceacam1 deletion on renal expression of all RAS components, PI3K phosphorylation, inflammation, and fibrosis.

scholarly journals The Effect of Angiotensin-Converting Enzyme Inhibition Using Captopril on Energy Balance and Glucose Homeostasis

Endocrinology ◽  
2009 ◽  
Vol 150 (9) ◽  
pp. 4114-4123 ◽  
Author(s):  
Annette D. de Kloet ◽  
Eric G. Krause ◽  
Dong-Hoon Kim ◽  
Randall R. Sakai ◽  
Randy J. Seeley ◽  
...  
Keyword(s):  
Body Weight ◽  
Glucose Tolerance ◽  
Angiotensin Converting Enzyme ◽  
High Fat Diet ◽  
Renin Angiotensin System ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Converting Enzyme ◽  
High Fat ◽  
Angiotensin System ◽  
Converting Enzyme Inhibition

Abstract Increasing evidence suggests that the renin-angiotensin-system contributes to the etiology of obesity. To evaluate the role of the renin-angiotensin-system in energy and glucose homeostasis, we examined body weight and composition, food intake, and glucose tolerance in rats given the angiotensin-converting enzyme inhibitor, captopril (∼40 mg/kg · d). Rats given captopril weighed less than controls when fed a high-fat diet (369.3 ± 8.0 vs. 441.7 ± 8.5 g after 35 d; P < 0.001) or low-fat chow (320.1 ± 4.9 vs. 339.8 ± 5.1 g after 21 d; P < 0.0001). This difference was attributable to reductions in adipose mass gained on high-fat (23.8 ± 2.0 vs. 65.12 ± 8.4 g after 35 d; P < 0.0001) and low-fat diets (12.2 ± 0.7 vs. 17.3 ± 1.3 g after 21 d; P < 0.001). Rats given captopril ate significantly less [3110.3 ± 57.8 vs. 3592.4 ± 88.8 kcal (cumulative 35 d high fat diet intake); P < 0.001] despite increased in neuropeptide-Y mRNA expression in the arcuate nucleus of the hypothalamus and had improved glucose tolerance compared with free-fed controls. Comparisons with pair-fed controls indicated that decreases in diet-induced weight gain and adiposity and improved glucose tolerance were due, primarily, to decreased food intake. To determine whether captopril caused animals to defend a lower body weight, animals in both groups were fasted for 24 h and subsequently restricted to 20% of their intake for 2 d. When free food was returned, captopril and control rats returned to their respective body weights and elicited comparable hyperphagic responses. These results suggest that angiotensin-converting enzyme inhibition protects against the development of diet-induced obesity and glucose intolerance.

Role of bradykinin in angiotensin-converting enzyme knockout mice

2003 ◽  
Vol 284 (6) ◽  
pp. H1969-H1977 ◽  
Author(s):  
Hong D. Xiao ◽  
Sebastien Fuchs ◽  
Justin M. Cole ◽  
Kevin M. Disher ◽  
Roy L. Sutliff ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Knockout Mice ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Low Blood Pressure ◽  
Urine Concentrating Ability

Angiotensin-converting enzyme (ACE) plays a central role in the renin-angiotensin system. Whereas ACE is responsible for the production of angiotensin II, it is also important in the elimination of bradykinin. Constitutively, the biological function of bradykinin is mediated through the bradykinin B2 receptor. ACE knockout mice have a complicated phenotype including very low blood pressure. To investigate the role of bradykinin in the expression of the ACE knockout phenotype, we bred B2 receptor knockout mice with ACE knockout mice, thus generating a line of mice deficient in both the B2 receptor and ACE. Surprisingly, these mice did not differ from ACE knockout mice in blood pressure, urine concentrating ability, renal pathology, and hematocrit. Thus abnormalities of bradykinin accumulation do not play an important role in the ACE knockout phenotype. Rather, this phenotype appears due to the defective production of angiotensin II.

scholarly journals Many Faces of Renin-angiotensin System - Focus on Eye

2017 ◽  
Vol 11 (1) ◽  
pp. 122-142 ◽  
Author(s):  
Mervi Holappa ◽  
Heikki Vapaatalo ◽  
Anu Vaajanen
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Anterior Part ◽  
Regulatory System ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Aqueous Humor Dynamics

The renin-angiotensin system (RAS), that is known for its role in the regulation of blood pressure as well as in fluid and electrolyte homeostasis, comprises dozens of angiotensin peptides and peptidases and at least six receptors. Six central components constitute the two main axes of the RAS cascade. Angiotensin (1-7), an angiotensin converting enzyme 2 and Mas receptor axis (ACE2-Ang(1-7)-MasR) counterbalances the harmful effects of the angiotensin II, angiotensin converting enzyme 1 and angiotensin II type 1 receptor axis (ACE1-AngII-AT1R) Whereas systemic RAS is an important factor in blood pressure regulation, tissue-specific regulatory system, responsible for long term regional changes, that has been found in various organs. In other words, RAS is not only endocrine but also complicated autocrine system. The human eye has its own intraocular RAS that is presente.g.in the structures involved in aqueous humor dynamics. Local RAS may thus be a target in the development of new anti-glaucomatous drugs. In this review, we first describe the systemic RAS cascade and then the local ocular RAS especially in the anterior part of the eye.

scholarly journals Pathological Role of Angiotensin II in Severe COVID-19

TH Open ◽  
2020 ◽  
Vol 04 (02) ◽  
pp. e138-e144 ◽  
Author(s):  
Wolfgang Miesbach
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Treatment Options ◽  
Renin Angiotensin System ◽  
Target Cells ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Novel Coronavirus

AbstractThe activated renin–angiotensin system induces a prothrombotic state resulting from the imbalance between coagulation and fibrinolysis. Angiotensin II is the central effector molecule of the activated renin–angiotensin system and is degraded by the angiotensin-converting enzyme 2 to angiotensin (1–7). The novel coronavirus infection (classified as COVID-19) is caused by the new coronavirus SARS-CoV-2 and is characterized by an exaggerated inflammatory response that can lead to severe manifestations such as acute respiratory distress syndrome, sepsis, and death in a proportion of patients, mostly elderly patients with preexisting comorbidities. SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptor to enter the target cells, resulting in activation of the renin–angiotensin system. After downregulating the angiotensin-converting enzyme 2, the vasoconstrictor angiotensin II is increasingly produced and its counterregulating molecules angiotensin (1–7) reduced. Angiotensin II increases thrombin formation and impairs fibrinolysis. Elevated levels were strongly associated with viral load and lung injury in patients with severe COVID-19. Therefore, the complex clinical picture of patients with severe complications of COVID-19 is triggered by the various effects of highly expressed angiotensin II on vasculopathy, coagulopathy, and inflammation. Future treatment options should focus on blocking the thrombogenic and inflammatory properties of angiotensin II in COVID-19 patients.

Resveratrol ameliorates the cyclosporine-induced vascular and renal impairments: possible impact of the modulation of renin–angiotensin system

2019 ◽  
Vol 97 (12) ◽  
pp. 1115-1123 ◽  
Author(s):  
Seldag Bekpinar ◽  
Ece Karaca ◽  
Selin Yamakoğlu ◽  
F. İlkay Alp-Yıldırım ◽  
Vakur Olgac ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Immunosuppressive Drug ◽  
Oxidative Stress Marker ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
System Components ◽  
Renal Tubular

Cyclosporine, an immunosuppressive drug, exhibits a toxic effect on renal and vascular systems. The present study investigated whether resveratrol treatment alleviates renal and vascular injury induced by cyclosporine. Cyclosporine (25 mg/kg per day, s.c.) was given for 7 days to rats either alone or in combination with resveratrol (10 mg/kg per day, i.p.). Relaxation and contraction responses of aorta were examined. Serum levels of blood urea nitrogen, creatinine, angiotensin II, and angiotensin 1-7 were measured. Histopathological examinations as well as immunostaining for 4-hydroxynonenal and nitrotyrosine were performed in the kidney. RNA expressions of renin–angiotensin system components were also measured in renal and aortic tissues. Cyclosporine decreased the endothelium-dependent relaxation and increased vascular contraction in the aorta. It caused renal tubular degeneration and increased immunostaining for 4-hydroxynonenal, an oxidative stress marker. Cyclosporine also caused upregulations of the vasoconstrictive renin–angiotensin system components in renal (angiotensin-converting enzyme) and aortic (angiotensin II type 1 receptor) tissues. Resveratrol co-treatment prevented the cyclosporine-related deteriorations. Moreover, it induced the expressions of vasodilatory effective angiotensin-converting enzyme 2 and angiotensin II type 2 receptor in aorta and kidney, respectively. We conclude that resveratrol may be effective in preventing cyclosporine-induced renal tubular degeneration and vascular dysfunction at least in part by modulating the renin–angiotensin system.

scholarly journals Association of seven renin angiotensin system gene polymorphisms with restenosis in patients following coronary stenting

2017 ◽  
Vol 18 (1) ◽  
pp. 147032031668877 ◽  
Author(s):  
Min Zhu ◽  
Minjun Yang ◽  
Jiangbo Lin ◽  
Huanhuan Zhu ◽  
Yifei Lu ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Neointimal Hyperplasia ◽  
Renin Angiotensin System ◽  
Coronary Stenting ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Stent Restenosis ◽  
In Stent Restenosis

Background and objective: Percutaneous coronary intervention, despite being effective for coronary revascularization, causes in-stent restenosis due to neointimal hyperplasia in a large number of patients. The renin-angiotensin system is involved in neointimal hyperplasia. This study sought to evaluate seven gene polymorphisms of key renin-angiotensin system components, including angiotensinogen, angiotensin-converting enzyme and angiotensin II type 1a receptors, and their associations with in-stent restenosis in patients with coronary artery disease following coronary stenting. Methods and results: Three hundred and fifty-two patients undergoing coronary drug-eluting stent implantation were recruited. Seventy-five patients (21.3%) were diagnosed as restenosis by angiography. Genotyping for angiotensin-converting enzyme insertion/deletion demonstrated a significant association of angiotensin-converting enzyme DD genotype with the occurrence of restenosis. Direct DNA sequencing revealed no association of angiotensinogen (M235T, G217A, G152A, G-6A, and A-20C) or angiotensin II type I receptor A1166C polymorphisms with in-stent restenosis. However, angiotensin II type 1a A1166C polymorphism was significantly associated with increased susceptibility to restenosis in a subgroup of patients aged more than 60 years. Conclusion: Thus, our study suggests that genetic polymorphisms of angiotensin-converting enzyme insertion/deletion are associated with in-stent restenosis in coronary artery disease patients following coronary stenting.

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