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Ace inhibitors and dose response

Jingni Wei, Hui Xu, Yinyin Liu, Baiyu Li, Fuxiang Zhou
The pathophysiological mechanism involved in the sustained endothelial secretion of cytokines that leads to fibrosis 6-16 months after radiotherapy remains unclear. Angiotensin II (Ang II) is produced by the endothelium in response to stressing stimuli, like radiation, and may induce the synthesis of TGF-β, a profibrotic cytokine. In this study we tested the hypothesis that captopril, an angiotensin-converting enzyme (ACE) inhibitor, inhibits or attenuates radiation-induced endothelial TGF-β1 secretion. The human endothelial hybrid cell line EA...
February 15, 2017: Oncotarget
Kevin Shee, Alan T Kono, Susan P D'Anna, Mark A Seltzer, Xiaoying Lu, Todd W Miller, Mary D Chamberlin
Despite the clinical efficacy of anthracycline agents such as doxorubicin, dose-limiting cardiac toxicities significantly limit their long-term use. Here, we present the case of a 33-year-old female patient with extensive metastatic ER+/PR+/HER2- mucinous adenocarcinoma of the breast, who was started on doxorubicin/cyclophosphamide therapy after progressing on paclitaxel and ovarian suppressor goserelin with aromatase inhibitor exemestane. The patient was comanaged by cardiology, who carefully monitored measures of cardiac function, including EKGs, serial echocardiograms, and profiling of lipids, troponin, and pro-BNP every 2 months...
September 2016: Case Reports in Oncology
Neha Rani, Saurabh Bharti, Ameesha Tomar, Amit Kumar Dinda, D S Arya, Jagriti Bhatia
Oxidative stress-induced PARP activation has been recognized to be a main factor in the pathogenesis of cisplatin-induced nephrotoxicity. Accumulating literature has revealed that ACE inhibitors may exert beneficial effect in several disease models via preventing PARP activation. Based on this hypothesis, we have evaluated the renoprotective effect of enalapril, an ACE inhibitor, and its underlying mechanism(s) in cisplatin-induced renal injury in rats. Male Albino Wistar rats were orally administered normal saline or enalapril (10, 20 and 40 mg/kg) for 10 days...
2016: Free Radical Research
Milton Packer
Angiotensin receptor-neprilysin inhibition has been shown to be superior to target doses of an ACE inhibitor in reducing the risk of cardiovascular death and clinical disease progression in patients with chronic heart failure and a reduced EF. Nevertheless, although sacubitril/valsartan has been available in the USA for a year, uptake of the drug by practitioners has been slow, in part because of misconceptions about the pivotal trial that demonstrated its efficacy in heart failure (PARADIGM-HF). This review addresses questions that have been raised in the USA about the design of the trial as well as the patients who were studied, the replicability and applicability of the results, and the safety of neprilysin inhibition...
October 2016: European Journal of Heart Failure
Mahesh Kumar Seth, M Ejaz Hussain, Santosh Pasha, Mohammad Fahim
Nitric oxide (NO) is a widespread biological mediator involved in many physiological and pathological processes, eg, in the regulation of vascular tone and hypertension. Chronic inhibition of NO synthase by N(G)-nitro-l-arginine methyl ester (l-NAME) hydrochloride results in the development of hypertension accompanied by an increase in vascular responsiveness to adrenergic stimuli. Recently, we developed a novel sulfur-containing angiotensin-converting enzyme inhibitor: 3-(3-thienyl)-l-alanyl-ornithyl-proline (TOP)...
2016: Drug Design, Development and Therapy
Yehuda Handelsman, Robert R Henry, Zachary T Bloomgarden, Sam Dagogo-Jack, Ralph A DeFronzo, Daniel Einhorn, Ele Ferrannini, Vivian A Fonseca, Alan J Garber, George Grunberger, Derek LeRoith, Guillermo E Umpierrez, Matthew R Weir
AACE = American Association of Clinical Endocrinologists ACE = American College of Endocrinology DKA = diabetic ketoacidosis EMA = European Medicines Agency FDA = U.S. Food and Drug Administration SGLT-2 = sodium glucosecotransporter 2 T1D = type 1 diabetes T2D = type 2 diabetes.
June 2016: Endocrine Practice
Samuel McGrath, Angharad Thomas, David Angelo Gorard
A 57-year-old man with iron deficiency anaemia developed general malaise, exertional dyspnoea and features of cardiac failure out of proportion to his anaemia (haemoglobin 120 g/L). Investigations showed a severely dilated left ventricle with an ejection fraction of 15%, due to dilated cardiomyopathy. He was treated with high-dose diuretics, ACE inhibitors and β-blocker therapy. Subsequent investigation into his iron deficiency anaemia revealed a new diagnosis of coeliac disease. After starting a gluten-free diet, his cardiac function improved markedly, with ejection fraction reaching 70%, allowing his cardiac medications to be withdrawn...
March 14, 2016: BMJ Case Reports
Tim A D Smith, Su M Phyu, Emmanuel U Akabuogu
BACKGROUND: Anticancer drug treatment, particularly with anthracyclines, is frequently associated with cardiotoxicity, an effect exacerbated by trastuzumab. Several compounds are in use clinically to attenuate the cardiac-damaging effects of chemotherapy drugs, including angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, the anti-diabetic drug metformin, and dexrazoxane. However, there is concern that the cardiac-preserving mechanisms of these drugs may also limit the anticancer efficacy of the chemotherapeutic agents...
January 2016: Anticancer Research
Ana Muñoz, María Esgueva, Manuel Gómez-Díez, Juan Manuel Serrano-Caballero, Cristina Castejón-Riber, Juan Manuel Serrano-Rodríguez
Changes in blood pressure (BP) during acute hypertension in response to angiotensin-converting enzyme inhibitors (ACEIs) have not been investigated in normotensive horses. In this study, six healthy horses were subjected to five trials, consisting in a treadmill exercise workload of 8 m/s for 1 min, 2 h after oral administration (PO) of placebo (0 mg/kg), enalapril (2.0 mg/kg), quinapril (1.0 mg/kg), ramipril (0.2 mg/kg) or benazepril (0.5 mg/kg). Serum angiotensin converting enzyme (ACE) activity was measured and systolic (SBP) and diastolic (DBP) blood pressures were recorded at rest (R), 2 h after placebo or ACEI administration (pre-E) and within the first 20 s after exercise (post-E)...
February 2016: Veterinary Journal
L Sulzberger, R Baillie, T Itinteang, S de Jong, R Marsh, P Leadbitter, S T Tan
The role of the renin-angiotensin system (RAS) in the biology of infantile haemangioma (IH) and its accelerated involution induced by β-blockers was first proposed in 2010. This led to the first clinical trial in 2012 using low-dose captopril, an angiotensin-converting enzyme (ACE) inhibitor, demonstrating a similar response in these tumours. This study aimed to compare serial serum levels of the components of the RAS in patients before and after surgical excision, propranolol or captopril treatment for problematic proliferating IH...
March 2016: Journal of Plastic, Reconstructive & Aesthetic Surgery: JPRAS
Valentina Fabiano, Carla Carnovale, Marta Gentili, Sonia Radice, Gian Vincenzo Zuccotti, Emilio Clementi, Cristiana Perrotta, Chiara Mameli
The use of angiotensin converting enzyme (ACE) inhibitors in combination with diuretics is a common strategy used for the treatment of patients affected by heart failure. An infant affected by initial congestive cardiac failure, after starting the treatment with enalapril in association with furosemide, developed acute kidney injury (AKI). No underlying renal disease or renal artery stenosis was found. He recovered from kidney injury after the therapy was suspended, thus suggesting that the drug combination is responsible for the onset of the adverse reaction...
2016: Pharmacology
Lixin Na, Xia Chu, Shuo Jiang, Chunjuan Li, Gang Li, Ying He, Yuanxiu Liu, Ying Li, Changhao Sun
PURPOSE: Vinegar has been reported to lower blood pressure, but its mechanism is unclear. This study explored whether vinegar plays antihypertensive effect by activating AMP-activated protein kinase (AMPK) pathway. METHODS: Male spontaneously hypertensive rats (SHRs) were assigned to vinegar, acetic acid, nifedipine, nifedipine + vinegar, or distilled water by oral gavage for 8 weeks. Blood and aortas were analyzed for biochemical indices and protein expression levels...
April 2016: European Journal of Nutrition
Li-Ting Ho, Lian-Yu Lin, Yao-Hsu Yang, Cho-Kai Wu, Jyh-Ming Jimmy Juang, Yi-Chih Wang, Chia-Ti Tsai, Ling-Ping Lai, Juey-Jen Hwang, Fu-Tien Chiang, Jiunn-Lee Lin, Pau-Chung Chen
OBJECTIVES: The objective is to assess the effectiveness of statin use to prevent atrial fibrillation (AF) in dialysis patients. METHODS: We used a database from the Registry for Catastrophic Illness from the National Health Research Institute (NHRI), which encompasses almost 100% of the patients receiving dialysis started from 1997 to 2008 in Taiwan. All dialysis patients aged 18 or older without history of cardiovascular events in 1997 and 1998 were incorporated...
December 15, 2015: International Journal of Cardiology
Dick de Zeeuw, Pirow Bekker, Elena Henkel, Christopher Hasslacher, Ioanna Gouni-Berthold, Heidrun Mehling, Antonia Potarca, Vladimir Tesar, Hiddo J Lambers Heerspink, Thomas J Schall
BACKGROUND: Patients with type 2 diabetes and nephropathy have high cardiorenal morbidity and mortality despite optimum treatment including angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). Residual risk is related to residual albuminuria. We assessed whether CCX140-B, a selective inhibitor of C-C chemokine receptor type 2 (CCR2), could further reduce albuminuria when given in addition to standard care, including ACE inhibitors or ARBs. METHODS: In this randomised, double-blind, placebo-controlled clinical trial, we recruited patients from 78 research centres in Belgium, Czech Republic, Germany, Hungary, Poland, and the UK...
September 2015: Lancet Diabetes & Endocrinology
Bryan Williams, Thomas M MacDonald, Mark Caulfield, J Kennedy Cruickshank, Gordon McInnes, Peter Sever, David J Webb, Jackie Salsbury, Steve Morant, Ian Ford, Morris J Brown
INTRODUCTION: Resistant hypertension is inadequately controlled blood pressure (BP) despite treatment with at least three BP-lowering drugs. A popular hypothesis is that resistant hypertension is due to excessive Na(+)-retention, and that 'further diuretic therapy' will be superior to alternative add-on drugs. METHODS AND ANALYSIS: Placebo-controlled, random crossover study of fourth-line treatment when added to standard (A+C+D) triple drug therapy: ACE inhibitor or Angiotensin receptor blocker (A) +Calcium channel blocker (C)+Diuretic (D)...
August 7, 2015: BMJ Open
Hatem Hamood, Rola Hamood, Manfred S Green, Ronit Almog
BACKGROUND: The extent to which drug adherence may be affected by patient characteristics remains unclear. This study investigated potential determinants of adherence to evidence-based cardioprotective medications in patients with acute myocardial infarction. DESIGN: Patient-based retrospective cohort study of 4655 elderly one-year survivors of acute myocardial infarction, members of a health organization in Israel, between 2005 and 2010. METHODS: All patients filled at least one prescription for any key medication...
June 2016: European Journal of Preventive Cardiology
Anna Starus, Boguslaw Nocek, Brian Bennett, James A Larrabee, Daniel L Shaw, Wisath Sae-Lee, Marie T Russo, Danuta M Gillner, Magdalena Makowska-Grzyska, Andrzej Joachimiak, Richard C Holz
Binding of the competitive inhibitor L-captopril to the dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase from Neisseria meningitidis (NmDapE) was examined by kinetic, spectroscopic, and crystallographic methods. L-Captopril, an angiotensin-converting enzyme (ACE) inhibitor, was previously shown to be a potent inhibitor of the DapE from Haemophilus influenzae (HiDapE) with an IC50 of 3.3 μM and a measured Ki of 1.8 μM and displayed a dose-responsive antibiotic activity toward Escherichia coli...
August 11, 2015: Biochemistry
Hatem Hamood, Rola Hamood, Manfred S Green, Ronit Almog
PURPOSE: Our aim is to estimate the effect of nonadherence to evidence-based cardioprotective medications on all-cause mortality in survivors of acute myocardial infarction (AMI). METHODS: A patient-based retrospective cohort study of 1-year survivors of AMI, members of a health organization in Israel, between 2005 and 2010 was used. Adherence was measured using the proportion-of-days-covered metric and defined as a proportion of days covered ≥80%. In order to determine the independent impact of medication nonadherence on all-cause mortality, Cox proportional hazards models were constructed, adjusting for patient demographic and clinical characteristics...
October 2015: Pharmacoepidemiology and Drug Safety
Yi-Ning Dai, Jing-Hua Wang, Jin-Zhou Zhu, Jie-Qiong Lin, Chao-Hui Yu, You-Ming Li
PURPOSE: We aim to investigate the association between angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) therapy and colorectal cancer (CRC) by conducting a systematic review with meta-analysis. METHODS: Literature was searched on PubMed, Scopus, and the Cochrane library to identify relevant studies evaluating ACEIs/ARBs therapy and risk of CRC incidence or survival of CRC patients. Pooled risk ratio (RR) with 95% confidence intervals was calculated for the association between ACEIs/ARBs and CRC risk and mortality...
September 2015: Cancer Causes & Control: CCC
Justin A Edward, Edward A Pankey, Ryan C Jupiter, George F Lasker, Daniel Yoo, Vishwaradh G Reddy, Taylor C Peak, Insun Chong, Mark R Jones, Samuel V Feintech, Sarah H Lindsey, Philip J Kadowitz
The kallikrein-kinin system is expressed in the corpus cavernosa, and bradykinin (BK) relaxes isolated corpora cavernosal strips. However, erectile responses to BK in the rat have not been investigated in vivo. In the present study, responses to intracorporal (ic) injections of BK were investigated in the anesthetized rat. BK, in doses of 1-100 μg/kg ic, produced dose-related increases in intracavernosal pressure (ICP) and dose-related deceases in mean arterial pressure (MAP). When decreases in MAP were prevented by intravenous injections of angiotensin II (Ang II), increases in ICP, in response to BK, were enhanced...
August 1, 2015: American Journal of Physiology. Heart and Circulatory Physiology
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