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)

1. Cardiovascular effects of opioid peptide products of proenkephalin, [Met] enkephalin (ME), [Leu] enkephalin (LE), [Met] enkephalyl Arg6-Phe7 (MEAP) and [Met] enkephalyl Arg6-Gly7-Leu8 (MEAGL) have been studied in urethane-anaesthetised rats. 2. ME, LE, MEAP and MEAGL produced vasodepression and bradycardia mediated by mu-opioid receptors. 3. Atypical responses to MEAP were observed in a quarter of the animals studied showing tachycardia and pressor effects. This response was probably due to the release of the dipeptide Arg-Phe which exerted its effects at sympathetic ganglia. 4. Studies with the peptidase inhibitors captopril and bestatin showed a differential potentiation of the cardiovascular effects of the proenkephalin products by inhibition of angiotensin converting enzyme and aminopeptidase. 5. The effects of vagotomy, pithing and studies with atropine, and N-methyl levallorphan were used to demonstrate that, for all four proenkephalin peptides, cardiovascular effects were mediated by peripheral opioid receptors and transmission to the CNS via vagal afferents.
Gen Pharmacol 1992 Mar
PMID:Mechanisms involved in the cardiovascular responses to opioid products of proenkephalin in the anaesthetised rat. 163 41

1. Bradykinin (cumulative concentrations of 0.007-0.09 micrograms ml-1) produced a dose-related, but statistically insignificant depression of the isometric contraction of the isolated, spontaneously beating atria of the guinea-pig. The same concentrations of bradykinin did not change the atrial rate, but a tendency to a slight decrease was observed. 2. Enalapril (4.06 or 13.54 mumol l-1), produced a dose-related potentiation of the effect of the highest concentration of bradykinin on the isometric contraction. 3. Captopril (equimolar concentrations) also potentiated the effect of the highest concentration of bradykinin on the isometric contraction. This effect of captopril was not dose-related. 4. Both enalapril and captopril did not change the effect of bradykinin on the heart rate. 5. Bradykinin induced dose-related hypotensive responses in anaesthetized cats (0.03-1.0 microgram/kg b.w., i.v.) with a tendency towards bradycardia. 6. Enalapril (0.3 and 1.0 mg/kg b.w., i.v.) significantly potentiated bradykinin-induced hypotension and bradycardia. However, the potentiating effect of enalapril was not dose-dependent. 7. Captopril (0.1, 0.3 and 1.0 mg/kg b.w., i.v.) significantly potentiated bradykinin-induced hypotension and bradycardia. Also, the potentiating effect of captopril was not dose-dependent. 8. The failure of ACE inhibitors to potentiate the cardiodepressant and hypotensive effects of bradykinin in a dose-dependent manner is explained with some other mechanism(s) independent of ACE inhibition.
Gen Pharmacol 1991
PMID:The potentiation of cardiodepressant and hypotensive effects of bradykinin by enalapril and captopril both in vitro and in vivo. 181 Aug 15

1. Streptozotocin diabetic rats were treated with captopril (50 mg l), an angiotensin converting enzyme-inhibitor, in drinking water for 20 weeks. 2. Systolic blood pressure and 24-hr urinary excretions of heparan sulfate and albumin were done at 2, 8, 16 and 20 weeks. 3. At the end of 20 weeks, all rats were killed, kidneys removed and glomeruli isolated. 4. Total glycosaminoglycan and heparan sulfate synthesis were determined by incubating glomeruli in the presence of 35S-sulfate. 5. Captopril significantly lowered blood pressure in diabetic rats 8 weeks after treatment. 6. Diabetic glomeruli synthesized less total glycosaminoglycan and heparan sulfate than glomeruli from nondiabetic rats. 7. Further characterization of heparan sulfate by ion-exchange chromatography showed that the fraction eluted with 1 M NaCl was significantly lower and the fraction eluted with 1.25 M NaCl significantly higher in diabetic than in normal rats. 8. Therapy with captopril normalized not only glomerular synthesis and content but also various fractions of heparan sulfate in diabetic rats. 9. Excretions of heparan sulfate and albumin were significantly higher in diabetic than in nondiabetic rats. 10. Captopril therapy did significantly lower but not normalize both these excretions in diabetic rats. 11. The data suggest that catopril therapy improves albuminuria through preservation of glomerular heparan sulfate and prevention of its urinary loss in diabetic rats.
Gen Pharmacol 1991
PMID:Prevention of albuminuria by captopril in diabetic rats. 205 28

1. An in vitro experiment was carried out to compare the inhibitory effect of SQ29,852 on human renal angiotensin converting enzyme (ACE) with those of captopril, enalapril and enalaprilat. 2. SQ29,852 strongly inhibited human renal ACE; its IC50 value was 1.5 x 10(-8) M. In terms of the IC50, SQ29,852's efficacy was about 1/10 of that of captopril and 1/28 of that of enalaprilat, but it was about 14 times more potent than enalapril. 3. SQ29,852 showed no inhibitory effects on cathepsin D, urinary kallikrein, renal renin, pepsin, trypsin and chymotrypsin. Its ACE-specificity was higher than that of captopril. 4. ACE inhibition by SQ29,852 was shown to be competitive, as revealed by Lineweaver-Burk plots. The affinity of SQ29,852 to ACE was shown to be high by a Ki value of 1.2 x 10(-8) M.
Gen Pharmacol 1990
PMID:Effect of SQ29,852, a new angiotensin converting enzyme (ACE) inhibitor with a phosphonic acid group, on the activity of angiotensin converting enzyme from human kidney. 216 61

Angiotensin I-converting enzyme activity was measured in homogenates of guinea pig (Cavia porcellus), chicken (Gallus domesticus), and carp (Cyprinus carpio) organs. The highest activity was found in guinea pig lung and chicken kidney. In carp the highest activity was found in heart and spleen, although gill arch also showed a high activity. Acute hypoxia decreased the angiotensin I-converting enzyme activity in guinea pig lung and carp gill arch, but the changes in chicken lung and kidney were considered nonsignificant.
Gen Comp Endocrinol 1990 Aug
PMID:Angiotensin-converting enzyme distribution and hypoxia response in mammal, bird, and fish. 216 64

1. In addition to their antihypertensive effect, ACE inhibitors have been reported to increase general well-being, general health and vitality and work performance. The cause of these effects is not known. A possible mechanism may be release of beta-endorphins. 2. In the present study changes in plasma concentration of beta-endorphins on days with ACE inhibitor treatment (n = 12) and on non-treatment control days (n = 12) were compared in 6 patients. 3. Both on control and treatment days the beta-endorphin level fell, by 7.1 and 10.0%, respectively, from 8.00 a.m. to 8.00 p.m., reflecting the known diurnal rhythm of this opioid. This difference between the control and treatment days is not statistically significant. 4. The study should be extended to determine endorphin concentration in the cerebrospinal fluid, and other opioids should be looked for.
Gen Pharmacol 1990
PMID:Effects of an angiotensin converting enzyme (ACE) inhibitor on plasma endorphin level. 217 36

The changes in arterial blood pressure and plasma cortisol concentration in response to exogenous angiotensin II (AII) and to manipulation of the endogenous renin-angiotensin system (RAS) have been examined in the flounder, Platichthys flesus. Intravenous [Asp1Val5]AII was pressor in a dose-dependent manner over the range of 0.25-250 micrograms/kg. Sequential blood sampling revealed steroidogenic stimulation, measured as change in plasma cortisol concentration, by doses of AII greater than 2.5 micrograms/kg. Enhanced circulating cortisol levels were measured some time after recovery of normal systemic blood pressure, suggesting that the change in plasma steroid concentration was not entirely dependent on the change in systemic blood pressure. Administration of the vasodilator papaverine produced immediate hypotension followed by gradual recovery in blood pressure, which was accompanied by a sustained increment in circulating cortisol. Both blood pressure recovery and the increased plasma steroid concentration were inhibited by prior treatment with the angiotensin converting enzyme inhibitor captopril. These results are consistent with a physiologically important role for the RAS in the control of plasma cortisol levels which complements its demonstrated pressor and dipsogenic actions in the flounder: the RAS may thus afford an integrating influence on the mechanisms of body fluid homeostasis in this euryhaline species.
Gen Comp Endocrinol 1990 Jun
PMID:The renin-angiotensin system and the regulation of plasma cortisol in the flounder, Platichthys flesus. 218 79

The lack of kinin formation in systemic circulation and in the renal system may lead to the pathogenesis of high blood pressure (hypertension). Angiotensin converting enzyme inhibitors are able to protect the kinin inactivation by kininase II, therefore, causing an accumulation of kinin. Although the concentrations of kinin in plasma after oral administration of ACE inhibitors are conflicting this is mainly due to methodological difficulties. Kinin receptor antagonists are becoming most reliable pharmacological probes for defining the molecular actions of kinin in several physiopathological states, and in the mechanism of actions of drugs which are dependent on the kinin system. The blood pressure lowering effect of ACE inhibitors can be antagonized by the pretreatment with kinin receptor antagonists. I have therefore proposed that the hypotensive action of ACE inhibitors may reflect the activation of kinin receptor. It is suggested that the development of compounds having protective properties on the kallikrein-kinin system might be therapeutically applicable as anti-hypertensive drugs.
Gen Pharmacol 1990
PMID:Does kinin mediate the hypotensive action of angiotensin converting enzyme (ACE) inhibitors? 219 99

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.
Gen Pharmacol 1990
PMID:Some behavioural effects of captopril in rats. 227 85

1. The effects of the angiotensin-converting enzyme (ACE) inhibitor lisinopril on plasma vasoactive intestinal polypeptides (VIP) and plasma noradrenaline, adrenaline and dopamine were studied in 12 patients with congestive heart failure over two consecutive 48-hr periods. The first day in each period served as a treatment day and the second as a control day. 2. A parallel monitoring was made of various hormonal parameters related to the renin-angiotensin-aldosterone system, and a right-heart catheter was used to monitor haemodynamics at rest. 3. Potent inhibition of the renin-system (as demonstrated by decreases in angiotensin converting enzyme (ACE) activity, angiotensin II and plasma aldosterone) together with improved haemodynamics (decreases in mean right atrial pressure, mean pulmonary arterial pressure, mean pulmonary capillary wedge pressure and mean systemic arterial pressure) were recorded. 4. Plasma VIP was significantly increased by a mean of 20.3% (P less than 0.01) on the lisinopril treatment days compared with the control days, whereas circulating catecholamines showed no significant pattern of change. 5. It is postulated that the potent vasodilatory neuromodulator VIP is implicated in the ACE inhibitor effects. 6. The ACE is a non-specific peptidase that previously has been implicated in the potentiation of other vasoactive endogenous systems (kinins and enkephalins).
Gen Pharmacol 1987
PMID:Increase in vasoactive intestinal polypeptides (VIP) by the angiotensin converting enzyme (ACE) inhibitor lisinopril in congestive heart failure. Relation to haemodynamic and hormonal changes. 282 21


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