Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies have demonstrated that Fischer-344 rats from Japanese Charles River Inc. specifically lack dipeptidyl(amino)peptidase IV (DAP IV-negative; EC 3.4.14.5), whereas Fischer-344 rats from sources within the United States (DAP IV-positive) possess normal DAP IV activity. In the present study, plasma from DAP IV-positive rats metabolized substance P (SP) (5.37 +/- 0.25 nmol/min/ml) via the actions of angiotensin-converting enzyme (EC 3.4.15.1) (1.86 +/- 0.50 nmol/min/ml) and DAP IV (2.56 +/- 0.42 nmol/min/ml). DAP IV sequentially converted SP to SP[3-11] and SP[5-11]. The SP[5-11] metabolite was then rapidly hydrolyzed by plasma aminopeptidase M (AmM; EC 3.4.11.2) (36.2 +/- 4.2 nmol/min/ml). In contrast, SP metabolism by plasma from DAP IV-negative rats was less than half that of control animals (2.14 +/- 0.06 nmol/min/ml), due to a complete lack of DAP IV hydrolysis. The absence of DAP IV was not associated with any differences in angiotensin-converting enzyme-mediated hydrolysis of SP (1.45 +/- 0.11 nmol/min/ml) or AmM-mediated hydrolysis of SP[5-11] (37.1 +/- 0.9 nmol/min/ml). Consistent with this deficiency in SP metabolism, SP was more potent in vivo in stimulating salivary secretion in DAP IV-negative rats compared to DAP IV-positive animals. Potentiation was specific in that SP[5-11], an SP fragment resistant to DAP IV, was equipotent in DAP IV-negative and positive animals. SP[5-11]-induced salivary secretion was potentiated in both strains when AmM-mediated hydrolysis was inhibited by amastatin (20 nmol/min, i.v.). These data provide direct evidence for a significant role for DAP IV and AmM in the in vivo processing of SP and active SP metabolites.
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PMID:Dipeptidyl(amino)peptidase IV and aminopeptidase M metabolize circulating substance P in vivo. 137 50

In addition to plasma metabolism of substance P (SP) by angiotensin converting enzyme (ACE; EC 3.4.15.1) (less than 1.0 nmol/min/ml), the majority of SP hydrolysis by rat and human plasma was due to dipeptidyl(amino)peptidase IV (DAP IV; EC 3.4.14.5) (3.15-5.91 nmol/min/ml), which sequentially converted SP to SP(3-11) and SP(5-11). In turn, the SP(5-11) metabolite was rapidly hydrolyzed by rat and human plasma aminopeptidase M (AmM; EC 3.4.11.2) (24.2-25.5 nmol/min/ml). The Km values of SP for DAP IV and of SP(5-11) for AmM ranged from 32.7 to 123 microM. In contrast, neurokinin A (NKA) was resistant to both ACE and DAP IV but was subject to N-terminal hydrolysis by AmM (3.76-10.8 nmol/min/ml; Km = 90.7 microM). These data demonstrate differential processing of SP and NKA by specific peptidases in rat and human plasma.
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PMID:Differential processing of substance P and neurokinin A by plasma dipeptidyl(amino)peptidase IV, aminopeptidase M and angiotensin converting enzyme. 172 23

Dipeptidyl(amino)peptidase IV (DAP IV; EC 3.4.14.5) and post proline cleaving enzyme (PPCE; EC 3.4.21.26) can convert or degrade vasoactive peptides and have been identified in isolated vessels. The present study examined the cellular (endothelial/smooth muscle) localization of vascular DAP IV and PPCE. Membrane-bound DAP IV was higher on cultured hog aorta smooth muscle (11.7 +/- 1.7 nmol/min/mg) than on endothelium (1.5 +/- 0.3 nmol/min/mg). In contrast, comparable levels of cytosolic PPCE were found in endothelium and smooth muscle (1.5 +/- 0.3 and 1.8 +/- 0.3 nmol/min/mg, respectively). DAP IV was specifically inhibited by diprotin A (Ile-Pro-Ile) (IC50 = 6 microM) while PPCE was inhibited by TPCK. Neither enzyme was affected by o-phenanthroline or inhibitors of aminopeptidase M (amastatin, bestatin), neutral endopeptidases (phosphoramidon), carboxypeptidases N (MERGETPA) or ACE (captopril). DAP IV may play a role in the extracellular metabolism of peptides at or near endothelial and smooth muscle cell surface receptors. In contrast, the cytosolic localization of PPCE may limit its participation to intracellular peptide metabolism.
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PMID:Dipeptidyl(amino)peptidase IV and post proline cleaving enzyme in cultured endothelial and smooth muscle cells. 257 34

Antisera raised against specific renal brush border peptidases have been used to characterize vascular surface membrane angiotensin I converting enzyme (ACE; EC 3.4.15.1), aminopeptidase M (AmM; EC 3.4.11.2), and dipeptidyl(amino)peptidase IV (DAP IV; EC 3.4.14.5) by techniques of differential solubilization, fused-rocket immunoelectrophoresis and crossed immunoelectrophoresis. The vascular membrane-bound enzymes are immunologically indistinguishable from their brush border counterparts and can be solubilized by treatment with detergent and/or papain. The electrophoretic mobilities of the papain-treated forms of each enzyme were greater than those of the detergent-treated forms. This increased mobility is associated with the removal of small, hydrophobic, non-antigenic components of the enzymes. Regardless of the method of solubilization, the electrophoretic mobilities of the vascular enzymes were greater than those of the brush border enzymes. However, after treatment with neuraminidase to remove sialic acid, their respective mobilities were similar. The mobilities of serum AmM and DAP IV were identical to the respective papain-solubilized vascular enzymes both before and after neuraminidase. Thus, like the brush border enzymes, the data presented are consistent with the model that vascular ACE, AmM and DAP IV are intrinsic membrane peptidases bound to their surface membranes by small, non-antigenic, hydrophobic anchors associated with the lipid bilayer. In addition, these vascular surface membrane peptidases are similar to and may be a source of the circulating enzymes.
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PMID:Immunoelectrophoretic analysis of vascular, membrane-bound angiotensin I converting enzyme, aminopeptidase M, and dipeptidyl(amino)peptidase IV. 614 48

Analysis of SP and NKA metabolism by human vascular endothelium, relative to that in human plasma, identified integrative, multiple pathways for the processing of circulating SP (but not NKA) by angiotensin-converting enzyme (ACE; EC 3.4.15.1), dipeptidyl(amino)peptidase IV (DAP IV; EC 3.4.14.5), and aminopeptidase M (AmM; EC 3.4.11.2). In contrast, SP and NKA, which may diffuse into or be neurally released within the vessel wall, were both metabolized by smooth muscle neutral endopeptidase-24.11 (NEP-24.11; EC 3.4.24.11). Collectively, these studies indicate peptide-specific and site-specific differential processing of SP and NKA by human plasma and vasculature.
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PMID:Metabolism of substance P and neurokinin A by human vascular endothelium and smooth muscle. 752 48

Hypertensive patients undergoing hemodialysis (HPH) have a marked impairment of their large artery distensibility and an increased cardiovascular morbidity. We investigated twelve HPH (8 males, 4 females, 53 +/- 12 years of age, +/- SD) following a single dose of an ACE inhibitor (quinapril 20 mg) comparatively to a placebo in a randomised cross over study over a week (H0 to H172). We measured repeatedly blood pressure and aortic distensibility (carotid-femoral pulse wave velocity, PWV). Statistical analysis was made through repeated measure ANOVA and repeated measure analysis of covariance because of the tight link between pressure and arterial function. Blood pressure decreased (SAP: p < 0.01, DAP: p < 0.001), and PWV was significantly improved independently of the pressure decrease. ACE inhibitor reduces blood pressure in these patients and improves large arterial function independently of the blood pressure changes.
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PMID:[Pressure-independent improvement of aortic distensibility in hypertensive hemodialysed patients]. 775 59

We have measured haemodynamic responses to induction of anaesthesia, laryngoscopy and intubation in 103 mild-moderate hypertensive patients (83 patients (diastolic pressures < or = 110 mm Hg) currently receiving one of four monotherapies (ACE inhibitors, group A; beta adrenoceptor blocking drugs, group B; calcium channel antagonists, group C; diuretics, group D) and 24 were untreated hypertensive patients). Anaesthesia was induced with fentanyl 1.5-2.0 micrograms kg-1 and thiopentone 3-5 mg kg-1. Tracheal intubation was facilitated by vecuronium 0.1 mg kg-1 and anaesthesia maintained with enflurane and nitrous oxide in oxygen. Systolic and diastolic pressures (SAP, DAP) were measured at 1-min intervals by a non-invasive oscillometric method and cardiac output (CO) and stroke volume (SV) by thoracic bioimpedance. Induction of anaesthesia was associated with a decrease in SAP, DAP and CO in groups A-D (P < 0.05). Heart rate (HR) decreased in groups A and D (P < 0.01) and systemic vascular resistance (SVR) decreased in groups A and B (P < 0.05). SAP and HR increased in all groups after laryngoscopy and intubation (P < 0.01) as did SVR in groups A, B and D (P < 0.02). CO was unaltered. Similar changes occurred in the untreated hypertensive patients, although nine of 24 patients exhibited HR > or = 100 beat min-1 after laryngoscopy and intubation. Comparison of the changes in SAP, DAP, CO and SVR with time showed no differences in the five treatment groups; changes in HR were significantly less in group B compared with the other groups (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Does the choice of antihypertensive therapy influence haemodynamic responses to induction, laryngoscopy and intubation? 794 53

The aim of the study was to evaluate the effect of angiotensin converting enzyme inhibition on blood pressure and plasma renin activity (PRA) in patients with essential (EH) and renovascular (RVH) hypertension. Forty patients with RVH and sixty four with EH were studied. All patients underwent renal digital subtraction angiography in order to find out renal artery stenosis. Blood pressure was measured before and 15, 30, 45, 60 and 90 minutes after captopril administration in the captopril test. PRA was determined before and 60 minutes after captopril. It was shown that fall of systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressure after captopril was significant in each time period both in EH and RVH. Hypotensive effect was significantly higher (p < 0.001) in RVH. Basic PRA did not differ in the studied groups. 60 minutes after captopril administration PRA was significantly higher (p < 0.001) in patients with RVH. Absolute and percentage rise of PRA also differentiated studied groups (p < 0.001). Significant correlations were found between the change of PRA after captopril and fall of SAP, DAP and MAP in both groups. These relationships were stronger in RVH.
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PMID:[Usefulness of converting enzyme inhibitors in diagnosis of renovascular hypertension. I. Comparison of the effect of angiotensin converting enzyme inhibition on blood pressure and plasma renin activity in patients with primary hypertension and renovascular hypertension]. 938 Aug 5

The aim of the study was to evaluate the effect of angiotensin converting enzyme inhibition on renoscintigraphic curves using DTPA as a tracer in patients with essential (EH) and renovascular (RVH) hypertension. Twenty four patients with EH and sixteen with RVH were studied. Protocol consisted of control renoscintigraphy with DTPA and the second one after captopril administration in dose 25 mg performed after three days. Relative DTPA uptake of the single kidney was calculated from the curve time-activity between 120 and 180 second after tracer administration. Results were expressed as a quotient of the relative DTPA uptake of ischemic or "weaker" kidney to the DTPA uptake of both kidneys (coefficient A) or contralateral one (coefficient B). Coefficient A in basic renoscintigraphy did not differ in patients with EH and RVH and was 45.81 +/- 3.02% and 44.66 +/- 6.17% respectively. In renoscintigraphy with captopril coefficient A decreased significantly (P < 0.001) in patients with RVH and was significantly lower (p < 0.05) than in patients with EH. Change (delta) of coefficient B after captopril was significantly higher in patients with RVH (p < 0.001). Significant correlations were found between delta coefficient A and delta diastolic (DAP) and mean (MAP) arterial pressure as well as delta plasma renin activity (PRA) after captopril in patients with RVH. Similarly, relationships were shown between percentage change (% delta) of coefficient B and % delta of systolic (SAP), DAP and MAP as well as delta PRA after captopril in patients with RVH.
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PMID:[Usefulness of angiotensin converting enzyme inhibitors in the diagnosis of renovascular hypertension. II. Comparison of the effect of angiotensin converting enzyme inhibition on reno-scintigraphic curves with DTPA in patients with essential and renovascular hypertension]. 948 Apr 62

The aim of our study was to examine the use of pharmacological therapy and to evaluate the economical aspects of treating hypertension (HT) in elderly patients in Poland. Two hundred and sixty eight elderly persons (147 females, 121 males; mean age: 72.2 +/- 6.0 years) were selected from Polish population by stratified and cluster random sampling with quotas. BP measurement was performed 3 times every 2 minutes at respondents home. In the questionnaire, awareness of HT was assessed. Prevalence of hypertension among subjects aged 65 years and over by JNC VI criteria (SAP > or = 140 mm Hg, DAP > or = 90 mm Hg or hypotensive therapy) was 74%. Awareness of HT was equal to 61%. Eleven percent of all hypertensives were well controlled. Among hypertensives, 71% took prescribed antihypertensive drugs on a regular basis. Patients with HT were taking the following antihypertensive drugs: diuretics 16%, diuretics and reserpine 20%, beta-blockers 19%, ACE inhibitors 53%, calcium antagonists 30%, and other 3%. Newer drugs were prescribed in 7%, and multi-source (generic) products in 93%. The average cost of treatment with one drug was 147 PLN (37.5 USD) per year (newer drugs: 413 PLN; multi-source product 126 PLN). Assuming those data and number of elderly people in Poland (4.335 mln), we estimated that 3.208 mln of subjects have had hypertension according to JNC VI criteria. Only 1.957 mln of patients with HT have been detected and only 0.353 mln of hypertensives have been well controlled. The approximate global cost of antihypertensive drugs per year in elderly patients in Poland has been equal to 285 mln PLN (72.8 mln USD). In hypothetical situation with optimal (100%) detection and control of HT the global cost by the actual rate of regularity in taking drugs would increase to 569 mln PLN (145.3 mln USD). The prevalence of HT in elderly people in Poland is very high. In elderly hypertensives ACE inhibitors are used most often. More than 90% of prescribed drugs are multi-source products. An optimal improvement of HT detection and control would cause a two-fold augmentation of the costs of pharmacological therapy.
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PMID:[Pharmacotherapy of arterial hypertension and pharmacoeconomic aspects of hypotensive therapy in elderly patients in Poland]. 1094 86


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