An enzyme in microsomal fraction of kidney that inactivates bradykinin

doi:10.1016/0024-3205(67)90090-2

Life Sciences

Volume 6, Issue 6, 15 March 1967, Pages 569-574

https://doi.org/10.1016/0024-3205(67)90090-2 Get rights and content

Abstract

The separation of an enzyme from the microsomal fraction of homogenized swine kidney is described. It is called peptidase P and hydrolyzes the ProPhe bond in bradykinin and related peptides.

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Angiotensin-converting enzyme
2023, Metalloenzymes: From Bench to Bedside
Angiotensin-converting enzyme (ACE) is a zinc-containing metallopeptidase, best known for its role in the conversion of Ang I in the active peptide Ang II, which plays a pivotal role in the blood pressure (BP) regulation trough the renin-angiotensin system (RAS). In the past decades, RAS has been deeply studied in all its aspects and implications. It has been seen that ACE and its substrates are involved in many other physiological and pathological processes in addition to pressure control, such as hematopoiesis, reproduction, renal development, and immune response. Its homologous protein ACE2, critical enzyme in counter-regulatory response to RAS, was studied, and its pharmacological modulation has been evaluated. According to ACE in vivo roles and its implication in a great number of physiological pathways, several studies focused on the potential role of classic ACE inhibitors (ACEIs) and new domain-selective compounds for the treatments of several diseases. This chapter seeks to review the evolution of the physio/pathological roles of ACEs and their pharmacological modulation, for the treatment of a wide range of pathologies.
Preoperative angiotensin converting enzyme inhibitor usage in patients with chronic subdural hematoma: Associations with initial presentation and clinical outcome
2016, Journal of Clinical Neuroscience
Citation Excerpt :
Fujisawa et al. showed that the activation of the kallikrein-kinin system in cSDH patients causes increasing vascular permeability with subsequent hematoma enlargement due to blood extravasation from neomembranes [13]. The rationale to investigate angiotensin converting enzyme (ACE) inhibitors in the setting of cSDH is that ACE inhibitors are known to cause elevated levels of bradykinin [14,15], the end-product of the kallikrein-kinin system that has been linked to enlargement of cSDH hematoma volume. The existing literature on the association between ACE inhibitors and cSDH is scarce and results have been mixed [16,17].
The aim of this study is to analyze the association of preoperative usage of angiotensin converting enzyme (ACE) inhibitors with the initial presentation and clinical outcome of patients with chronic subdural hematoma (cSDH). Patients treated for cSDH between 2009 and 2013 at our institution were included in this retrospective case-control study. Medical charts were reviewed retrospectively and data were analyzed using descriptive and inferential statistics. Out of 203 patients (58 females, mean age 73.2 years), 53 (26%) patients were on ACE inhibitors before their presentation with cSDH. Median initial hematoma volume in individuals with ACE inhibitors (179.2 ± standard error of the mean [SEM] 13.0 ml) was significantly higher compared to patients without ACE inhibitors (140.4 ± SEM 6.2 ml; p = 0.007). There was an increased probability of surgical reintervention in the ACE inhibitor group (12/53, 23% versus 19/153, 12%; p = 0.079), especially in patients older than 80 years (6/23, 26% versus 3/45, 7%; p = 0.026). ACE inhibitors are associated with higher hematoma volume in patients with cSDH and with a higher frequency of recurrences requiring surgery (especially in the very old). We hypothesize that these effects are due to ACE inhibitor induced bradykinin elevation causing increased vascular permeability of the highly vascularized neomembranes in cSDH.
Antihypertensive effect of novel angiotensin I converting enzyme inhibitory peptide from chum salmon (Oncorhynchus keta) skin in spontaneously hypertensive rats
2014, Journal of Functional Foods
Citation Excerpt :
Its treatment is effective in reducing the risk of cardiovascular disease including arteriosclerosis, stroke and myocardial infarction (Sheih, Fang, & Wu, 2009). Angiotensin converting enzyme (ACE) catalyzes the production of angiotensin II (Ang II) from angiotensin I (Ng & Vane, 1968), and degrade bradykinin (Skeggs, Marsh, Khan, & Shumway, 1954), which result in the elevation of blood pressure (Erdos & Yang, 1967; Yang & Erdos, 1967; Yang, Erdos, & Levin, 1971). The conversions of both of these substrates are domain-dependent as the N-terminal domain of somatic ACE cleaves the terminal dipeptide of bradykinin and the C-terminal domain produces Ang II (Igic, Nakajima, Yeh, Sorrells, & Erdos, 1973).
Angiotensin I converting enzyme (ACE) inhibitory peptide was separated from chum salmon (Oncorhynchus keta) skin hydrolysate prepared by various hydrolysis enzymes. The trypsin hydrolysate had the highest ACE inhibitory activity compared to the other hydrolysates. We attempted to isolate ACE inhibitory peptides from trypsin hydrolysate using chromatograph methods. The purified peptide was identified as Gly-Leu-Pro-Leu-Asn-Leu-Pro (M.W. 770 Da) and IC₅₀ value was 18.7 μM. We synthesized ACE inhibitory peptides (Gly-Leu-Pro, Asn-Leu-Pro, Gly-Leu, and Leu-Pro) based on sequences of purified peptide from chum salmon skin. Among the synthesized peptides, the Gly-Leu-Pro had the highest ACE inhibitory activity. Furthermore, antihypertensive effect in spontaneously hypertensive rats also revealed that oral administration of synthesized ACE inhibitory peptide (Gly-Leu-Pro) can decrease systolic blood pressure significantly. Our study suggests that novel ACE inhibitory peptides derived from chum salmon skin may be beneficial as anti-hypertensive compounds for use as functional food ingredients.
Plasminogen activator inhibitor-1 and angiotensin converting enzyme gene polymorphisms in Turkish asthmatic children
2013, Allergologia et Immunopathologia
Citation Excerpt :
Another candidate gene proposed to be involved in the pathogenesis of asthma is angiotensin converting enzyme (ACE) gene. Angiotensin converting enzyme plays an essential role in the metabolism of angiotensin II (AT II) and inactivates bradykinins and tachykinins which are bronchoconstrictors and also mediators of inflammation in asthma.12 Angiotensin II is also involved in the pathogenesis of asthma by interaction with airway smooth muscle.
Polymorphisms of plasminogen activator inhibitor-1 (PAI-1) and angiotensin-converting enzyme (ACE) genes have been implicated in susceptibility to asthma. In this study, we aimed to investigate whether there was any association between childhood asthma and polymorphisms of the PAI-1 and ACE genes.
Two hundred and three Turkish children aged 5–15 years, including 102 asthmatic patients and 101 healthy control subjects were included in this study. The asthma group was divided into two groups as follows: Group I: Asthmatic children with positive family history for atopy (n = 53), Group II: Asthmatic children without any family history for atopy (n = 49). One hundred and twenty-eight atopic family members were also included in the study. The insertion/deletion (I/D) polymorphism of the ACE and PAI-1 4G/5G gene polymorphisms was carried out by polymerase chain reaction.
The prevalence of the PAI-1 4G allele was significantly greater in asthmatic children compared to control group (p < 0.05, OR: 1.64 (1.11–2.43)) but there was no significant relation between ACE I/D genotypes and childhood asthma. No significant difference was detected between Groups I and II in terms of these ACE and PAI-1 genotypes and allele frequencies. No significant relationship was found between both gene polymorphisms and total serum IgE and skin prick test results.
It has been established that PAI-1 4G allele may be a genetic risk factor for childhood asthma but ACE gene I/D polymorphisms do not play a role in the development of asthma in the sample of Turkish children.
Evaluation of angiotensin converting enzyme gene polymorphism and susceptibility to bronchial asthma among Egyptians
2012, Allergologia et Immunopathologia
Citation Excerpt :
Angiotensin converting enzyme (ACE) gene is one of these genes. ACE is expressed at high levels in the lungs, and exhibits an anti-inflammatory effect through catabolising bradykinins and tachykinins, which induce smooth muscle airway constriction, bronchial edema, mucus hyper-secretion, and neurogenic inflammation.5 On the other hand, ACE converts angiotensin I into the vasoactive angiotensin II, which through causing proliferation and contractility of airway smooth muscles, can contribute to excessive airway obstruction.6
Angiotensin converting enzyme (ACE) is expressed at high levels in the lungs and plays a role in the metabolism of the endogenous peptides involved in asthma pathogenesis. ACE gene polymorphisms have been reported to be linked to asthma. However, the results are conflicting, with no reported studies on Egyptian asthmatics. We aimed to assess ACE gene polymorphism among Egyptian asthmatics, and to determine its possible association with asthma severity.
This case–control study was conducted on 30 adult asthmatic patients, and 30 healthy controls with no history of asthma or atopy. Atopic status among asthmatics was determined by skin prick test (SPT). Lung functions were assessed by spirometry. Determination of ACE genotypes was performed for all subjects. Total serum IgE levels were measured by ELISA.
The frequencies of the DD, ID and II genotypes were 46.7%, 40%, and 13.3%, respectively among the cases, and 33.3%, 40%, and 26.7%, respectively among the controls. No significant differences in ACE genotype distribution were observed between cases and controls (p = 0.37). Genotype distribution did not differ according to age of onset or severity of asthma, total serum IgE levels, SPT positivity, or number of positive SPT reactions. Furthermore, ACE polymorphism was not statistically different between asthmatic patients without any associated atopic disease and those with an associated atopic disease.
The results of our study indicate that ACE gene polymorphism is not significantly associated with bronchial asthma or with its severity among Egyptian adults.
Combination inhibition of the renin-angiotensin system: Is more better
2011, Kidney International
Angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers are considered the standard of care for treatment of cardiovascular disease and chronic kidney disease. Combination therapy with both angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers effectively inhibits the renin–angiotensin system as well as potentiates the vasodilatory effects of bradykinin. It has been advocated that this dual blockade approach theoretically should result in improved clinical outcomes in both cardiovascular disease and chronic kidney disease. Clinical trial evidence for the use of combination therapy with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in cardiovascular disease has provided conflicting results in hypertension, congestive heart failure, and ischemic heart disease. Clinical trial evidence to support combination therapy with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in chronic kidney disease has largely been based on proteinuria reduction as a surrogate marker for clinically meaningful outcomes. Recent large-scale randomized clinical trials have not been able to validate protection in halting progression in chronic kidney disease with a dual blockade approach. This review serves as an appraisal on the clinical evidence of combination angiotensin-converting enzyme inhibition and angiotensin II receptor blockade in both cardiovascular disease and chronic kidney disease.

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^☆: Supported in part by Grant HE 08764 from the National Institutes of Health, U.S.P.H.S.

^☆☆: Presented in part in the III International Pharmacological Congress, Sao Paulo 1966.

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An enzyme in microsomal fraction of kidney that inactivates bradykinin☆,☆☆

Abstract

J. Biol. Chem.

Advances in Pharmacology