Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of NO-formation induced by accumulated endogenous bradykinin (BK) via local ACE-inhibition with ramiprilat (RT) or by adding BK exogenously was evaluated in cultured bovine aortic endothelial cells (BAEC) and in isolated rat hearts with post-ischaemic reperfusion injuries. Furthermore we used the n-octyl-ester of ramipril (RA-octil) which was shown to have no ACE-inhibitory action. In BAEC, ACE-inhibition by RT (1 x 10(-8)-1 x 10(-6) mol/l) or addition of BK (1 x 10(-8)-1 x 10(-6) mol/l) stimulated the formation of NO and prostacyclin (PGI2) as assessed by endothelial cyclic GMP- and 6-keto-PGF1a formation. Cyclic GMP and PGI2 synthesis was completely suppressed by the NO synthase inhibitor NG-nitro-L-arginine (L-NNA, 1 x 10(-5) mol/l) and by the B2 kinin receptor antagonist HOE 140 (1 x 10(-7) mol/l). RA-octil (1 x 10(-8)-1 x 10(-4) mol/l) did not affect endothelial cyclic GMP production in BAEC. In isolated working rat hearts subjected to local ischemia with reperfusion both RT (1 x 10(-8) mol/l) and BK (1 x 10(-9) mol/l) reduced the incidence and duration of ventricular fibrillation. In parallel myocardial function (left ventricular pressure, coronary flow) and metabolism (high energy rich phosphates) were improved showing a comparable fingerprint for RT and BK. Addition of L-NNA (1 x 10(-6) mol/l) or HOE 140 (1 x 10(-9) mol/l) abolished these protective effects of RT and BK. As in the BAEC studies RA-octil was without beneficial effects on the isolated ischaemic rat heart. The findings on BAEC show that inhibition of ACE localized on the luminal side of the vascular endothelium results in increased synthesis of NO and prostacyclin by local accumulation of endothelium-derived BK. Similar mechanisms may occur in the ischaemic rat heart leading to cardioprotection.
...
PMID:ACE-inhibition induces NO-formation in cultured bovine endothelial cells and protects isolated ischemic rat hearts. 133 74

The high mortality rate from coronary heart disease in hypertensives can only be substantially reduced if sudden coronary death rates can be decreased. The aim of this review is to discuss how treatment may be tailored to reduce the risk of sudden death in high-risk patients. Clinical trials have not yet produced long-term primary prevention data on the effects of angiotensin converting enzyme (ACE) inhibitors, calcium antagonists or alpha-blockers on cardiovascular complications and sudden death in hypertensive patients. Further, the conclusion from large-scale secondary preventive studies presently available on ACE inhibitors and calcium antagonists is that their impact on sudden death has been disappointing. By contrast, some beta-blockers have reduced sudden death and other coronary events both in primary and secondary preventive studies. The benefits have been attributed to beta 1-blockade, and seem to be independent of blood pressure control. It cannot be assumed that all beta-blockers are equally effective in preventing ventricular fibrillation, sudden death and other coronary events. To date, the best documented data cover the lipophilic beta-blockers and it is speculated that by increasing levels of cardiac vagal tone and electrical stability in the heart, beta 1-blockade in the brain might contribute to the reduction in sudden death risk seen with these beta-blockers.
...
PMID:The role of beta receptor blockade in preventing sudden death. 809 50

Previous studies on the possible antiarrhythmic effects of angiotensin converting enzyme (ACE) inhibitors during early ischemia in pigs have been inconclusive or negative; however, proof of adequate ACE inhibition was not provided. Perindoprilat, 0.06 mg/kg, i.v., was administered 30 min prior to ligation of the anterior descending coronary artery (CAL) in anesthetised open-chest pigs. Plasma ACE activity was decreased by 95.0 +/- 1.9% when measured 5 min before CAL. Within 5 min of CAL, the ventricular fibrillation threshold (VFT) in the control group was decreased from 11.8 +/- 1.9 to 7.2 +/- 1.2 mA (p less than 0.01). Perindoprilat prevented the fall in the VFT and the increase in left ventricular end-diastolic pressure caused by CAL. Perindoprilat decreased arterial pressure. Cardiac output (thermodilution) was decreased by 23 +/- 3% after CAL in the control group and by only 10 +/- 5% (p less than 0.05) in the perindoprilat group (both versus pre-CAL values). In the control group cyclic AMP was increased from 0.97 +/- 0.04 (pre-CAL) to 1.16 +/- 0.04 nmol/g (p less than 0.05) in the central ischemic zone 20 min after CAL. Perindoprilat prevented this increase in cyclic AMP. Twenty minutes after CAL blood flow (microsphere method) in the nonischemic zone of the perindoprilat group was increased, whereas blood flow in the central ischemic zone was decreased compared to the control group. However, levels of tissue metabolites (ATP, phosphocreatine, lactate) measured in drill biopsies in the same zones of the two groups were similar.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Antiarrhythmic effects of the angiotensin converting enzyme inhibitor perindoprilat in a pig model of acute regional myocardial ischemia. 138 73

Sudden cardiac death (SCD) is usually due to monomorphic ventricular tachycardia and/or ventricular fibrillation. However, in the vast majority of patients these arrhythmias are associated with advanced structural disease. In our society, this is usually due to coronary artery disease (CAD). The implantable cardioverter--defibrillator is the logical approach to management in survivors of SCD. Its rational use must be guided by electrophysiology study. However, a realistic and cost-effective approach to the prevention of a first cardiac arrest must be multifaceted and take cognisance of other aspects including primary prevention. Limitation of the size of myocardial infarction (MI) is vital. Trials already suggests that effective thrombolysis may impinge long-term on arrhythmic end-points. Following infarction, ventricular arrhythmias and sudden death may also be decreased by aspirin, beta-blockers, and possibly angiotensin converting enzyme inhibitors and amiodarone. Many post-infarction studies employ a combined end-point of death and clinical arrhythmias. However, death is usually confined to those with an ejection fraction < 35%. In them, treatment of associated heart failure is often a consideration and if the ejection fraction < 15-20%, depending on donor availability, transplantation may even be the preferred therapeutic option to the cardioverter-defibrillator.
...
PMID:Prevention of sudden cardiac death: the ICD, or an electrical end-point with preceding opportunities for intervention? 144 53

To test the hypothesis that angiotensin II (Ang II) in the central nervous system modulates catecholamine-induced cardiac arrhythmias and to determine whether endogenous opioids are operative in this action, arrhythmias were produced in male Wistar rats, by continuous infusion of epinephrine at incremental doses until the development of fatal arrhythmias that were usually ventricular fibrillation. Rats were instrumented with catheters in the lateral cerebral ventricle, femoral vein and femoral artery. Ang II, 0.5 microgram, in the lateral cerebral ventricle (ICV) markedly and significantly (p less than 0.05) increased the epinephrine dose, at the occurrence of ventricular premature beats compared to the control group 228 +/- 11 (SEM) vs 116 +/- 7 micrograms epinephrine/kg and at the onset of fatal arrhythmias 225 +/- 13 vs 185 +/- 9 micrograms epinephrine/kg. Ang II, 0.5 microgram i.v., did not affect arrhythmia threshold. The angiotensin converting enzyme inhibitor captopril, 1 mg/kg, decreased arrhythmia threshold as ventricular arrhythmias were first noted at 106 +/- 4 and fatal arrhythmias occurred at 118 +/- 4 micrograms epinephrine/kg. The Ang II receptor antagonist saralasin 150 micrograms/kg ICV, blunted and 300 micrograms/kg ICV reversed the effect of Ang II. The mu opioids antagonist naloxone and the kappa opioid antagonist MR 2266, 50 micrograms/kg ICV, prevented the effect of Ang II on fatal arrhythmias. The action Ang II on arrhythmias could not be explained by the effects of Ang II on blood pressure or heart rate. These data indicate a role for Ang II within the CNS to modulate cardiac arrhythmias and that this is mediated in part, by endogenous opioids.
...
PMID:Angiotensin in the brain suppresses epinephrine-induced cardiac arrhythmias through CNS opioid mechanisms. 165 93

Local inhibition of angiotensin-converting enzyme (ACE, kininase II) produces both attenuation of angiotensin (Ang) II generation and bradykinin (BK) degradation. To delineate the participation of BK in the cardioprotective actions of ACE inhibitors, experiments were performed in rats and dogs with cardiac ischemia-reperfusion injuries. (I) In rat isolated perfused working hearts with regional myocardial ischemia, BK in concentrations as low as 1 X 10(-9) M increased coronary flow (CF) and reduced the incidence and duration of reperfusion ventricular fibrillation (VF). In addition, enzyme activities of lactate dehydrogenase (LDH) and creatine kinase as well as lactate output were decreased in the venous effluent of BK-perfused hearts, which also showed improved cardiodynamic and metabolic parameters. Even concentrations of BK lower than 1 X 10(-10) M, which were without influence on coronary flow, exerted comparable beneficial metabolic effects connected with reduced incidence and duration of VF. Combined perfusions with threshold concentrations of BK (1 X 10(-12) M) and the ACE inhibitor ramiprilat (2.58 X 10(-9) M), which were ineffective given alone, resulted in a marked cardioprotective effect. Perfusion with Ang II (1 X 10(-9) M) aggravated reperfusion arrhythmias and worsened myocardial metabolism. BK perfusion prevented this deterioration in a concentration-dependent manner, whereas the Ang II receptor antagonist saralasin was only marginally effective. The BK antagonist D-Arg-[Hyp2, Thi5,8, D-Phe7]-BK (1 X 10(-5) M) completely abolished the cardioprotective effects of BK or the ACE inhibitor. However, higher concentrations of BK (1 X 10(-7) M) or ramiprilat (2.58 X 10(-5) M) competitively reversed these properties of the BK antagonist. (II) In anesthetized dogs, BK was infused into the coronary artery in a dose of 1 ng/kg/min during occlusion (90 min) and reperfusion (30 min) of the left descending coronary artery (LAD)--a dose without effects on cardiovascular parameters. In line with the findings in isolated ischemic rat hearts, BK infusion reduced LDH activities and lactate concentrations in the coronary sinus blood, whereas myocardial tissue levels of glycogen and energy-rich phosphates were increased in the infarcted area. The cardioprotective effects produced by perfusion with BK or by reduction of BK degradation through local interference with ACE favor a role for BK in ischemia-reperfusion injuries in rats and dogs.
...
PMID:Local inhibition of bradykinin degradation in ischemic hearts. 169 70

A combination of oral flecainide and mexiletine was given to 11 patients in whom monotherapy with one of these drugs was ineffective for the suppression of inducible ventricular tachycardia or fibrillation. In eight of 11 studies, combination therapy prevented inducibility of a sustained ventricular tachycardia or resulted in induction of only nonsustained tachycardia (P = 0.0003, when compared to monotherapy). In one patient, a slow ventricular tachycardia was induced. During exercise testing ventricular tachycardia occurred in two of these nine patients, and ventricular fibrillation in another patient. Seven patients received combination on the long term, for a mean of 18 months. One patient had recurrences of ventricular tachycardia which was well tolerated. Another patient had a recurrent episode of ventricular fibrillation, but was successfully resuscitated. Severe congestive heart failure occurred in two patients. ACE inhibitors were given to them and to another four patients. No other important unwanted effects occurred. The combination of mexiletine and flecainide is very effective in suppressing inducible sustained ventricular tachycardia. The efficacy of this combination to prevent recurrences of ventricular tachyarrhythmias is acceptable. Exercise testing is of importance to unmask proarrhythmic effects before discharge from hospital.
...
PMID:Combination of flecainide and mexiletine for the treatment of ventricular tachyarrhythmias. 170 Mar 88

Local inhibition of angiotensin-converting enzyme (ACE, kininase II) produces both-attenuation of angiotensin II generation and of bradykinin degradation. To delineate the participation of bradykinin in the cardioprotective actions of ACE inhibitors, experiments were performed in rats and dogs with cardiac ischemia-reperfusion injuries. In isolated perfused working rat hearts with regional myocardial ischemia, bradykinin in concentrations as low as 1 x 10(-9) M increases coronary flow and reduces the incidence and duration of reperfusion ventricular fibrillation. In addition, enzyme activities of lactate dehydrogenase and creatine kinase as well as lactate output were decreased in the venous effluent of bradykinin-perfused hearts, which also showed improved cardiodynamic and metabolic parameters. Even concentrations of bradykinin lower than 1 x 10(-10) M, which were without influence on coronary flow, exerted comparable beneficial metabolic effects connected with reduced incidence and duration of ventricular fibrillation. Combined perfusions with threshold concentrations of bradykinin (1 x 10(-12) M) and the ACE inhibitor ramiprilat (2,58 x 10(-9) M), which were ineffective given alone, resulted in a marked cardioprotective effect. Perfusion with angiotensin II (1 x 10(-9) M) aggravated reperfusion arrhythmias and worsened myocardial metabolism. Bradykinin perfusion prevented this deterioration in a concentration-dependent manner. The bradykinin antagonist D-Arg-[Hyp2, Thi5,8, D-Phe7]-bradykinin (1 x 10(-5)) completely abolished the cardioprotective effects of bradykinin or the ACE inhibitor. However, higher concentrations of bradykinin (1 x 10(-7) M) or ramiprilat (2,58 x 10(-5) M) reversed these properties of the bradykinin antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:[ACE inhibition: mechanisms of "cardioprotection" in acute myocardial ischemia]. 186 30

The effects of the angiotensin converting enzyme (ACE) inhibitors captopril, enalapril, HOE 498, and its prodrug on reperfusion arrhythmias after 15 min of coronary ligation were investigated in the isolated rat heart. Drug concentrations were equipotent in their effect on angiotensin I pressor response. Furthermore, the effect of indomethacin on ACE inhibition with captopril was studied. Upon reperfusion, ventricular fibrillation occurred in all untreated hearts, in all prodrug HOE 498-treated hearts (15 micrograms/ml), and in 4 of 6 of the enalapril-treated (8 micrograms/ml) hearts. In contrast, in only 2 of 6 (p less than 0.002) of the HOE 498-treated hearts (15 micrograms/ml) and in none (p less than 0.001) of the captopril-treated hearts (80 micrograms/ml) did ventricular fibrillation occur. A massive purine overflow was observed in untreated hearts upon reperfusion. This overflow was significantly reduced by captopril and HOE 498, whereas enalapril and prodrug HOE 498 had no significant effect. Concomitantly, the pressure-rate index was severely impaired after 30 min of reperfusion in the untreated, enalapril, and prodrug HOE 498 groups (33 +/- 9, 52 +/- 11, and 48 +/- 12% of initial values, respectively), but captopril and HOE 498 significantly reduced the impairment of mechanical function (124 +/- 9% and 98 +/- 9%, respectively). In contrast to enalapril and prodrug HOE 498, captopril and HOE 498 markedly reduced noradrenaline overflow during the first minutes of reperfusion. No angiotensin II was detectable in the coronary effluent of untreated hearts.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Reduction of reperfusion arrhythmias in the ischemic isolated rat heart by angiotensin converting enzyme inhibitors: a comparison of captopril, enalapril, and HOE 498. 242 10

Based on our experience with the prospective follow-up study in a group of patients (n = 21) with congestive heart failure (CHF) (NYHA III n = 10, NYHA IV n = 11) and left ventricular ejection fraction below 30%, who were referred to our ordinary care unit by their family physicians after an initial work-up, we investigated the impact of a special treatment program in 25 patients with similar CHF despite therapy (60 +/- 4 years, NYHA III n = 11, NYHA IV n = 14, LVEF less than 30%, 17 +/- 3%). The program focused on three issues: (1) individualized medical therapy of CHF, (2) antiarrhythmic treatment and close follow-up visits, and (3) continuous education of patients and physicians in order to improve treatment compliance and the early management of complications. Medical treatment was based on diuretic and vasodilator therapy in all the patients, while positive inotropic substances including digoxin were given selectively. Vasodilator treatment was started with prazosin in 22 patients and with ACE inhibitors in three patients with low serum sodium. Fifty-five percent of the patients on prazosin had to be changed over to ACE inhibitors. Amiodarone was used as first line drug to treat symptomatic ventricular tachycardia in two patients and two survivors of ventricular fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Individualized care in patients with chronic congestive heart failure. 244 Dec 4


1 2 3 4 Next >>

---