Fetopathy associated with exposure to angiotensin converting enzyme inhibitors and angiotensin receptor antagonists
Department of Pediatrics, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9063, USA. Early Human Development
(Impact Factor: 1.79).
02/2006; 82(1):23-8. DOI: 10.1016/j.earlhumdev.2005.11.001
The renin-angiotensin system plays an important role in the regulation of blood pressure. The use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers both control hypertension by interruption of the production or action of angiotensin II, the major end-product of the renin-angiotensin system. The use of angiotensin converting enzyme inhibitors in pregnant women revealed serious and deleterious effects on fetal development including renal failure, renal dysplasia, hypotension, oligohydramnios, pulmonary hypoplasia, and hypocalvaria. The fetal effects of angiotensin converting enzyme inhibitors seem to be greatest during the 2nd and 3rd trimesters of pregnancy. The fetal effect of angiotensin converting enzyme inhibitors during the 1st trimester is controversial. These effects may represent the effect of hypoperfusion in the fetus and not a teratogenic effect. The effect of angiotensin receptor blockers is similar to converting enzyme inhibitors. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers should be avoided in all pregnant women. Alternative antihypertensive medications should be considered for use in women of childbearing years.
Available from: PubMed Central
- "The importance of the RAS in embryonic renal function is shown by the dramatic consequences of ACE inhibitor treatment during pregnancy. Congenital malformations have been reported in infants with fetal exposure during the first trimester alone (29) but the fetal effects of ACE inhibitors appear to be more marked during late pregnancy and are attributed to severe hypotension and renal hypoperfusion (30,31). The role of the RAS in human kidney development has been further documented by the reports of genetic RTD due to gene inactivation of any one of the major components of the RAS (18). "
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ABSTRACT: Renal tubular dysgenesis (RTD) is a recessive autosomal disease characterized most often by perinatal death. It is due to the inactivation of any of the major genes of the renin-angiotensin system (RAS), one of which is the angiotensin I-converting enzyme (ACE). ACE is present as a tissue-bound enzyme and circulates in plasma after its solubilization. In this report, we present the effect of different ACE mutations associated with RTD on ACE intracellular trafficking, secretion and enzymatic activity. One truncated mutant, R762X, responsible for neonatal death, was found to be an enzymatically active, secreted form, not inserted in the plasma membrane. In contrast, another mutant, R1180P, was compatible with life after transient neonatal renal insufficiency. This mutant was located at the plasma membrane and rapidly secreted. These results highlight the importance of tissue-bound ACE versus circulating ACE and show that the total absence of cell surface expression of ACE is incompatible with life. In addition two missense mutants (W594R, R828H) and two truncated mutants (Q1136X, G1145AX) were also studied. These mutants were neither inserted in the plasma membrane nor secreted. Finally, the structural implications of these ACE mutations were examined by molecular modeling, which suggested some important structural alterations such as disruption of intra-molecular non-covalent interactions (eg. salt bridges).
Human Molecular Genetics 10/2013; 23(6). DOI:10.1093/hmg/ddt535 · 6.39 Impact Factor
Available from: H P Vasantha Rupasinghe
- "Inhibition of ACE is a promising way of controlling the over activation of RAAS. There are prominent ACE inhibitory drugs currently in use for treatment of hypertension including Captopril, Rampiril and Enalpiril (Quan, 2006). However, research continues to investigate natural ACE inhibitors. "
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ABSTRACT: Hypertension is a major public health problem rising across the globe. Inhibition of angiotensin converting enzyme (ACE) is identified as a main therapeutic target in controlling high blood pressure. The present study investigated the ACE inhibitory property of a flavonoid-rich apple peel extract (FAE), its constituents, selected flavonoids and some quercetin metabolites using a biochemical assay of ACE inhibition and a human umbilical vein endothelial cell (HUVEC) model. FAE, all the tested flavonoids except genistein, and two quercetin metabolites (quercetin-3-O-glucuronic acid and quercetin-3-O-sulfate) significantly (p<0.05) inhibited ACE. Enzyme kinetic analysis revealed that flavonoids are competitive inhibitors of ACE. In the HUVEC model, FAE, quercetin-3-O-glucoside and quercetin-3-O-glucuronic acid inhibited significantly (p<0.05) ACE activity. Overall, FAE and most of the flavonoids tested showed ACE inhibition in vitro which needs further investigations using animal and human clinical trials.
Food Chemistry 12/2012; 135(4):2320-5. DOI:10.1016/j.foodchem.2012.07.023 · 3.39 Impact Factor
Available from: Geoffrey Lee
- "Patients had to be > 18 and < 85 years of age. Pre-menopausal women had to be on contraception in view of potential randomisation to losartan with its known teratogenic effects . Baseline echocardiography was required to demonstrate normal EF (defined as > 45%). "
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ABSTRACT: Haemodialysis results in a left ventricular hypertrophic response. It is unclear whether tight blood pressure control or particular medications might attenuate this response. We sought to determine, in a pre-dialysis cohort on atenolol, whether Losartan might attenuate left ventricular hypertrophy post arteriovenous fistula creation in end stage kidney disease.
Placebo controlled double blind randomisation of 26 patients to fixed dose atenolol plus fixed dose losartan or placebo occurred 1 day prior to fistula creation. Pre-randomisation echocardiography was repeated at 1 week and 1-month. Measurement was undertaken of blood pressure, heart rate, brain natriuretic peptide, serum creatinine and estimated glomerular filtration rate. The primary pre-specified endpoint was the change in left ventricular mass at 1 month. Non-parametric statistical comparison was performed within and between groups.
There was no difference in left ventricular mass between our groups 1-month post fistula creation. In the entire cohort, change in left ventricular mass was driven by changes in blood pressure and volume loading. Blood pressure changes correlated with left ventricular mass changes seen shortly post arteriovenous fistula creation, suggesting blood pressure control during this time period may be an important part of the management of end stage kidney disease.
We did not see an advantage with the use of losartan with respect to diminution of the LVM response. However, our demonstrated change in LVM was relatively small compared to previous literature and suggests a possible role for beta blockade as a neurohormonal modulator around the time of arteriovenous fistula creation.
Clinical trials.gov (NCT00602004).
BMC Research Notes 05/2012; 5:260. DOI:10.1186/1756-0500-5-260
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