scholarly journals IgE-Mediated Anaphylaxis to Foods, Venom, and Drugs: Influence of Serum Angiotensin Converting Enzyme Levels and Genotype

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
V. A. Varney ◽  
A. Warner ◽  
A. Ghosh ◽  
A. Nicholas ◽  
N. Sumar
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Healthy Controls ◽  
Cardiovascular Collapse ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Ace Genotype ◽  
Ige Mediated

Circulating angiotensin-II protects the circulation against sudden falls in blood pressure and is generated by the enzymatic action of angiotensin converting enzyme (ACE) on angiotensin-I. The ACE genes have 2 allelic forms, “I” and “D.” The “D” genotype has both highest angiotensin-II generation and serum ACE levels compared to “I”. 120 patients with IgE-anaphylaxis, 119 healthy controls, and 49 atopics had serum ACE levels, ACE genotype, and renin levels determined. Plasma renin levels were identical for all groups. Serum ACE levels and genotypes were similar for healthy controls (HC) and atopics, but lower in anaphylaxis (), with ACE genotypes also showing increased “I” genes (). This effect was more pronounced in subjects manifesting airway angioedema and cardiovascular collapse (AACVS) than mild cutaneous and respiratory (CRA) symptoms. AACVS was significantly associated with the presence of “I” genes. For “ID” genotype OR is 5.6, 95% CI 1.8 to 17.4, and for “II” genotype OR is 44, 95% CI 5 to 1891 within the anaphylaxis group = 0.001. The results show a difference in the genotype frequency between control and anaphylaxis, suggesting a role for the renin angiotensin system in anaphylaxis manifesting with airway angioedema and cardiovascular collapse.

Investigation of the Mechanism of β2-Agonist-Induced Activation of the Renin—Angiotensin System

1995 ◽  
Vol 88 (4) ◽  
pp. 433-437 ◽  
Author(s):  
Evelyn A. Millar ◽  
Gordon T. McInnes ◽  
Neil C. Thomson
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Serum Potassium ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Serum Angiotensin Converting Enzyme ◽  
Renin Angiotensin ◽  
Plasma Angiotensin

1. We have previously described activation of the renin—angiotensin system in asthma, and also by high-dose nebulized β2-agonists. In this study we sought to determine the mechanism responsible. 2. The influence of the angiotensin-converting enzyme inhibitor, lisinopril, on the response of the renin—angiotensin system and serum potassium to nebulized salbutamol was investigated in a randomized, double-blind, crossover study in eight healthy volunteers using a factorial block design. On study days, subjects received lisinopril 20 mg orally or identical placebo tablets followed 3 h later by nebulized salbutamol or placebo inhalation; plasma renin, angiotensin II, serum angiotensin-converting enzyme and potassium were measured at intervals for 120 min after inhalation. 3. Following salbutamol, plasma renin and angiotensin II concentrations were increased significantly compared with placebo [mean (SEM) plasma renin of 61.7 (15.6) μ-units/ml and angiotensin II of 17.7 (5.4) pg/mol 15 min after salbutamol, P < 0.05 versus placebo]. Baseline plasma renin concentrations were increased [160.1 (20.6) μ-units/ml] and baseline plasma angiotensin II concentrations were reduced [1.4 (0.1) pg/ml] by lisinopril, P < 0.05 versus placebo in each case. Inhibition of angiotensin-converting enzyme completely inhibited this salbutamol-induced rise in plasma angiotensin II [mean (SEM) plasma angiotensin II of 1.5 (0.4) pg/ml 15 min after salbutamol, P < 0.05 versus placebo] but had no effect on the changes in plasma renin concentrations after the β2-agonist [mean (SEM) plasma renin of 198.4 (18.9) μ-units/ml 15 min after salbutamol]. 4. Serum angiotensin-converting enzyme concentrations tended to increase throughout the study period following salbutamol compared with placebo, although this difference was not statistically significant. Lisinopril caused complete suppression of serum angiotensin-converting enzyme. 5. Salbutamol significantly reduced serum potassium concentrations [mean (SEM) baseline serum potassium of 4.26 (0.16) mmol/l decreasing to 3.08 (0.2) mmol/l at 45 min, P < 0.05 versus placebo]. Although lisinopril had no significant effect on serum potassium, the hypokalaemic response to salbutamol was significantly reduced in the presence of the angiotensin-convering enzyme inhibitor [mean (SEM) decrease in serum potassium of −1.2 (0.2) mmol/l compared with −0.8 (0.2) mmol/l, P < 0.05 versus placebo]. 6. Mean blood pressure was unaffected by active therapy. One subject experienced dizziness and headache after lisinopril. 7. The results of this study confirm that nebulized salbutamol causes activation of plasma renin and angiotensin II. Pretreatment with an angiotensin-converting enzyme inhibitor prevented the salbutamol-induced increase in plasma angiotensin II but not renin concentration. 8. We conclude that elevation of plasma angiotensin II induced by high-dose nebulized β2-agonists involves the classical components of the renin—angiotensin system including angiotensin-converting enzyme.

Effect of Hypoxia and β2-Agonists on the Activity of the Renin-Angiotensin System in Normal Subjects

1995 ◽  
Vol 89 (3) ◽  
pp. 273-276 ◽  
Author(s):  
Evelyn A. Millar ◽  
Robert M. Angus ◽  
Jane E. Nally ◽  
Robin Clayton ◽  
Neil C. Thomson
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Healthy Subjects ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Serum Angiotensin Converting Enzyme ◽  
Renin Angiotensin ◽  
Β2 Agonists

1. We have reported that the renin-angiotensin system is activated in acute asthma, and also by high-dose nebulized β2-agonists. The contribution of other possible stimuli such as hypoxia is unknown. The present study examined the effect of hypoxia alone and also combined with β2-agonists on the activity of the renin-angiotensin system. 2. In a double-blind crossover study, eight healthy subjects were randomized to inhale a hypoxic (FiO2 = 12%) or normoxic mixture for a period of 30 min, with either nebulized salbutamol (5 mg) or placebo administered into the circuit after 10 min. Plasma renin, angiotensin II and serum angiotensin-converting enzyme were measured at baseline and at intervals up to 2 h. Pulse rate and oxygen saturation were monitored continuously throughout the study. 3. After hypoxia alone, there was no change in the levels of plasma renin or angiotensin II. When salbutamol was added to the hypoxic mixture, there was a significant rise in plasma renin and angiotensin II [mean (SEM) maximal increase in angiotensin II of 5.6 (2.9)pg/ml and renin of 15.5 (6.3) μ-units/ml at 60 min, P < 0.05 compared with normoxia]. When salbutamol was administered in the normoxic mixture, plasma renin and angiotensin II also increased but this effect was similar to the effect of salbutamol in the hypoxic mixture. Serum angiotensin-converting enzyme levels were unaffected by hypoxia or salbutamol. 4. We conclude from these results that there is activation of the renin—angiotensin system in healthy subjects by salbutamol, but not hypoxia. In addition, the effect of salbutamol on the renin—angiotensin system is not influenced by the presence of hypoxia. As similar levels of hypoxia occur in acute exacerbations of asthma, it seems unlikely that hypoxia is contributing to activation of the renin—angiotensin system in acute severe asthma.

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.

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 Chymase-dependent production of angiotensin II: an old enzyme in old hearts

2017 ◽  
Vol 312 (2) ◽  
pp. H223-H231 ◽  
Author(s):  
Ghezal Froogh ◽  
John T. Pinto ◽  
Yicong Le ◽  
Sharath Kandhi ◽  
Yeabsra Aleligne ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Aged Rats ◽  
Converting Enzyme ◽  
Local Formation ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Age Dependent

Age-dependent alteration of the renin-angiotensin system (RAS) and generation of angiotensin II (Ang II) are well documented. By contrast, RAS-independent generation of Ang II in aging and its responses to exercise have not been explored. To this end, we examined the effects of chymase, a secretory serine protease, on the angiotensin-converting enzyme (ACE)-independent conversion of Ang I to Ang II. We hypothesized that age-dependent alteration of cardiac Ang II formation is chymase dependent in nature and is prevented by exercise training. Experiments were conducted on hearts isolated from young (3 mo), aged sedentary (24 mo), and aged rats chronically exercised on a treadmill. In the presence of low Ang I levels and downregulation of ACE expression/activity, cardiac Ang II levels were significantly higher in aged than young rats, suggesting an ACE-independent response. Aged hearts also displayed significantly increased chymase expression and activity, as well as upregulation of tryptase, a biological marker of mast cells, confirming a mast cell-sourced increase in chymase. Coincidently, cardiac superoxide produced from NADPH oxidase (Nox) was significantly enhanced in aged rats and was normalized by exercise. Conversely, a significant reduction in cardiac expression of ACE2 followed by lower Ang 1-7 levels and downregulation of the Mas receptor (binding protein of Ang 1-7) in aged rats were completely reversed by exercise. In conclusion, local formation of Ang II is increased in aged hearts, and chymase is primarily responsible for this increase. Chronic exercise is able to normalize the age-dependent alterations via compromising chymase/Ang II/angiotensin type 1 receptor/Nox actions while promoting ACE2/Ang 1-7/MasR signaling. NEW & NOTEWORTHY Aging increases angiotensin-converting enzyme (ACE)-independent production of cardiac angiotensin II (Ang II), a response that is driven by chymase in an exercise-reversible manner. These findings highlight chymase, in addition to ACE, as an important therapeutic target in the treatment and prevention of Ang II-induced deterioration of cardiac function in the elderly. Listen to this article's corresponding podcast @ http://ajpheart.podbean.com/e/renin-angiotensin-system-signaling-in-aged-and-age-exercised-rats/ .

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