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

Urine of untreated EHP was eluted, on a ion-exchange chromatography, in two protein peaks with ACE activity, at 0.7 mS (BI) and 1.25 mS (BII), while urine of treated EHP, was eluted only in one peak with ACE activity (0.7 mS). BI (Mr, 88 kDa) and BII (Mr, 61 kDa) convert AI to AII, hydrolyze bradikinin, are inhibited by captopril, EDTA and metal ions.
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PMID:Angiotensin converting enzymes from urine of treated and untreated essential mild hypertensive patients (EHP) with diuretic: partial purification and characterization. 133 55

The renin-angiotensin system has a varied role in the regulation of cardiac function, ranging from early receptor-mediated effects such as second messenger generation, to more delayed responses such as protein synthesis and cell growth. Clinically, the importance of the RAS in cardiovascular disease is becoming increasingly evident with the use of ACE inhibitors in treating various pathological processes. With evidence for the existence of a local RAS in the heart, the molecular and biochemical regulation of this system requires investigation. Much additional work needs to be directed toward elucidating the mechanisms by which the AII-receptor couples to cardiac growth, how the local RAS is regulated, and the nature of controls that modulate cardiac production and actions of this peptide. Increased understanding of the mechanisms by which AII actions are affected in cardiac tissue will likely lead to enhanced therapeutic modalities for the treatment of pathological cardiovascular conditions in which the RAS plays an integral role.
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PMID:Cardiac actions of angiotensin II: Role of an intracardiac renin-angiotensin system. 156 74

Non-peptide receptor ligands with differential affinity for the angiotensin II-1 (AII-1) receptor (EXP3312, EXP3880) or the AII-2 receptor (PD123177) and an angiotensin converting enzyme (ACE) inhibitor captopril were evaluated for the ability to protect against a renin-induced performance deficit in a passive avoidance (PA) task in rats. The ability to retain a PA response was shown to decrease as the dose of intracerebroventricularly (i.c.v.) administered renin increased with maximal retention deficits occurring at 1.0 micrograms/5 microliters i.c.v. EXP3312 (1-100 micrograms/5 microliters i.c.v.) and EXP3880 (1-100 micrograms/5 microliters i.c.v.) produced dose-dependent increases in retention latencies when co-administered with renin. The peak effect dose (PED) for EXP3312 and EXP3880 was 3 and 30 micrograms i.c.v., respectively. In contrast, PD123177 was not effective in preventing the renin-induced decrease in retention across a broad range of doses (0.1-100 micrograms/5 microliters i.c.v.). Captopril (1-100 micrograms/5 microliters i.c.v.) also prevented the renin-induced performance deficit with a PED of 30 micrograms/5 microliters i.c.v. These results suggest that renin given i.c.v. produces a deficit in performance of a PA response in rats and that this effect can be attenuated by an ACE inhibitor, AII-1 receptor ligands, but not AII-2 receptor blocker.
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PMID:Non-peptide angiotensin II receptor antagonist and angiotensin-converting enzyme inhibitor: effect on a renin-induced deficit of a passive avoidance response in rats. 180 40

The present study examined the presence and cellular distribution of angiotensinogen, the precursor to the angiotensin peptides, in the ovary of the normal cycling rat by immunocytochemistry. Angiotensinogen staining was present in the granulosa cells of maturing follicles and to a lesser extent in those undergoing atresia. Staining was not seen in the granulosa cells of primordial or early primary follicles. In maturing follicles intense staining for angiotensinogen was confined to the antral cell layers, cells of the cumulus oophorus and in the follicular fluid. Strong immunostaining was also seen in the germinal epithelium covering the ovary. Lighter angiotensinogen staining was observed in some parts of the cortical and medullary stroma and occasionally in corpora lutea. No variation in the intensity or pattern of angiotensinogen staining was observed throughout the estrous cycle. Comparison of the distribution of angiotensinogen with the previously described localization of renin, AII, angiotensin converting enzyme and AII receptors, suggests that there are a number of intra-ovarian sites at which AII could be produced.
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PMID:The immunocytochemical localization of angiotensinogen in the rat ovary. 220 93

Rat kidney slices were incubated with [3H]-noradrenaline and placed into a superfusion chamber between two platinum electrodes. The kidney slices accumulated and stored radioactivity. In kidney slices taken from rats whose sympathetic nerve terminals were destroyed by pretreatment with 6-hydroxydopamine accumulation of radioactivity was abolished. The alpha 2-adrenoceptor antagonist idazoxan (0.1-1 microM) enhanced but tetrodotoxin (TTX, 1 microM) or omission of calcium from the superfusion solution abolished the stimulation induced (S-I) outflow of radioactivity. Angiotensin (A) I (3-300 nM) and AII (1-100 nM) enhanced S-I outflow of radioactivity. The effect of AI was markedly attenuated by the angiotensin converting enzyme inhibitor captopril (3 microM) and that of AII was blocked by the AII receptor antagonist saralasin (1 microM). These results suggest that the kidney slice preparation is a valid technique to study modulation of renal noradrenaline release. Endogenous noradrenaline released from sympathetic nerves in rat kidney slices activates prejunctional alpha 2-adrenoceptors to inhibit its own release. AII, which can also be formed locally from AI in these kidney slices, activates prejunctional AII receptors to facilitate renal noradrenaline release.
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PMID:Modulation of noradrenaline release from rat cortical kidney slices: effects of angiotensin I and II. 226 7

1. Effects of inhibition of angiotensin converting enzyme (ACE, EC 3.4.15.1) in brain on psychomotor, exploratory, stereotyped and cognitive behaviour in rats were investigated. To inhibit brain ACE captopril (D-3-mercaptopropanoyl-L-proline) was given orally (p.o., 50 mg/kg) or intracerebroventricularly (i.c.v., 5 micrograms/rat). 3. Captopril given p.o. but not i.c.v. significantly enhanced stereotypy, overall number of conditioned avoidance responses, and decreased blood pressure. 4. No statistically significant influence of captopril given by either route on the number of crossings, rearings and bar approaches in the open field, performance of passive avoidance and number of correct choices as well as the speed of running for food in the T-maze was observed. 5. In conclusion, a small decrease of the activity of nigrostriatal dopaminergic system caused by the decrease of AII and/or increase of bradykinin, substance P, enkephalins and neurotensin in brain resulting from ACE inhibition is postulated.
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PMID:Some behavioural effects of captopril in rats. 227 85

Angiotensin II receptor and angiotensin converting enzyme distributions in the human medulla oblongata were localised by quantitative in vitro autoradiography. Angiotensin II receptors were labelled with the antagonist analogue 125I-[Sar1, Ile8] AII while angiotensin converting enzyme was labelled with 125I-351A, a derivative of the specific converting enzyme inhibitor, lisinopril. Angiotensin II receptor binding and angiotensin converting enzyme are present in high concentrations in the nucleus of the solitary tract, the dorsal motor nucleus of vagus, the rostral and caudal ventrolateral reticular nucleus, and in a band connecting the dorsal and ventral regions. In the rostral and caudal ventrolateral reticular nucleus, angiotensin II receptors are distributed in a punctate pattern that registers with neuronal cell bodies. The distribution and density of these cell bodies closely resemble those of catecholamine-containing neurones mapped by others. In view of the known interactions of angiotensin II with both central and peripheral catecholamine-containing neurons of laboratory animals, the current anatomical findings suggest similar interactions between these neuroactive compounds in the human central nervous system. The presence of angiotensin II receptors and angiotensin converting enzyme in the nucleus of the solitary tract, dorsal motor nucleus of vagus, and rostral and caudal ventrolateral reticular nucleus demonstrates sites for central angiotensin II to exert its known actions on vasopressin release and autonomic functions including blood pressure control. These data also suggest a possible interaction between angiotensin II and central catecholeminergic systems.
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PMID:Localization and characterization of angiotensin II receptor binding and angiotensin converting enzyme in the human medulla oblongata. 283 36

In order to investigate the role of plasma angiotensin I (pAI) converting enzyme on the activity of the renin-angiotensin system, we measured plasma renin activity (PRA), plasma angiotensin II (pAII), and plasma angiotensin I converting enzyme (pACE) activity in fourteen patients with essential hypertension before and after two hours of ambulation combined with intravenous furosemide administration. Significant increases were observed in the values of PRA (p less than 0.005), pAII (p less than 0.005) and ACE activity (p less than 0.05) after ambulation. The ratios of log pAII/log PRA were increased significantly after ambulation (p less than 0.005), and a significantly positive correlation was observed between log pAII/log PRA and ACE activity (p less than 0.01). These results suggested that not only PRA but also ACE activity contributed to the activity of renin-angiotensin system through the generation of AII.
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PMID:The role of plasma angiotensin I converting enzyme in regulation of renin-angiotensin system activity in patients with essential hypertension. 283 30

The formation of AII from a metabolite of AI, des-leu10-angiotensin I [A(1-9)] has been studied in centrifugal fractions of rat lung and kidney using gradient elution HPLC to monitor the formation of peptide products. AII-forming activity was present in kidney S2 (22.3 nmol/mg protein/min) but not in kidney P2 centrifugal fractions. Lung S2 fractions showed relatively weak AII-forming activity (0.34 nmole/mg protein/min) whilst no activity was observed in lung P2. Carboxypeptidase N-like activity measured using both Hipp-Arg and Hipp-Lys as synthetic substrates did not parallel AII-forming activity, since this activity was highest in the P2 fractions of both lung and kidney, as were ACE and aminopeptidase activities. Whilst the major peptide produced in kidney S2 was AII (71%) significant amounts of both AIII (23%) and A(2-9) (6%) were also observed. In lung the amounts of these peptides produced as a percentage of the A(1-9) degrading activity were 2.9%, 2.4% and 21% respectively. The AII-forming activity in kidney S2 was not inhibited by enalaprilat, bestatin, amastatin, phosphoramidon or Pro-Phe but was inhibited (31%) by 1 mM cobalt (II). 1,10-Phenanthroline, iodoacetic acid, EDTA and puromycin significantly enhanced the formation of AII and increased the rate of degradation of the substrate, A(1-9). These results support the concept of a sequential carboxypeptidase pathway operating, particularly in kidney, to produce AII from AI. These results provide further evidence of an alternative metabolic pathway for the formation of AII not involving angiotensin converting enzyme.
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PMID:Formation of angiotensin II and other angiotensin peptides from des-leu 10-angiotensin I in rat lung and kidney. 284 26

Results from both preclinical and clinical studies described here suggest that ACE may have a role in the modulation of cognitive memory processes in the rat and in humans. The finding of improved cognitive performance among patients treated with captopril relative to those treated with propranolol or methyldopa is consistent with other clinical and prec-clinical data. Clinical data derive primarily from quality of life measures based on interviews with patients in the same clinical trial from which our other cognitive data are drawn. For example, mental acuity in the workplace was reported to have improved significantly from baseline to week 24 in patients on captopril (p less than 0.05), although it did not change in patients treated with propranolol and worsened in those receiving methyldopa (Croog et al, 1987). The difference between captopril and methyldopa was significant (p less than 0.01). Pre-clinical data come primarily from studies demonstrating that inhibitors of ACE delay CAE in rats when compared not only with methyldopa, but also with saline (Sudilovsky et al, 1984, 1986). A fundamental question is how could inhibition of ACE improve cognitive functioning independent of blood pressure control. It is known that captopril exerts its antihypertensive effects primarily through inhibition of the ACE and that this is present in the brain as well as in non-neuronal tissues elsewhere (Ganten et al, 1982; Strittmatter et al, 1983, 1984). The activity of the enzyme has been found to be significantly increased in the caudate nucleus, the frontal cortex, parahyppocampal gyrus, and medial hippocampus of patients dying with Alzheimer's disease when compared to age-matched controls (Arregui et al, 1982). In addition, AII has been shown to impair performance on various learning and memory paradigms in animals (Melo and Graeff, 1975; Morgan and Routtenberg, 1977). Raising the level of endogenous AII by intravenous administration of its precursor renin has similar effects, and these are prevented if captopril is administered previously (Koller et al, 1979). Also, chronic oral treatment with captopril produces changes of brain renin angiotensin system parameters which suggest inhibition of AII biosyntheses in the brain (Scholkens et al, 1983). It is conceivable therefore, that our findings with prolonged administration of captopril are exerted through reduced formation of AII. Other possible mechanisms through which captopril may affect cognition include peptide-protein systems (Ganten et al, 1982, Sudilovsky et al, 1988) or the modulation of cerebral blood flow autoregulation mechanisms.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Angiotensin converting enzyme and memory: preclinical and clinical data. 285 49


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