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

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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)

ACE inhibitors have been proven to be effective in the reduction of ischemia/reperfusion damage after myocardial ischemia. In an attempt to investigate this effect in a model of syngeneic liver transplantation in the rat, we compared a control group with an ACE inhibitor treatment group, in which enalapril was given i.v. before and during reperfusion. By means of in vivo microscopy, sinusoidal perfusion rate, permanent leukocyte sticking in sinusoids and postsinusoidal venules, and leukocyte rolling in postsinusoidal venules were assessed. Liver function was evaluated by measuring bile output. The sinusoidal perfusion rate was significantly improved by enalapril treatment. Leukocyte sticking in both sinusoids and postsinusoidal venules was found to be remarkably reduced in enalapril-treated animals; the fraction of rolling leukocytes remained unchanged. Bile output was increased in enalapril-treated animals. These results demonstrated, in a model of rat liver transplantation, that ACE inhibition by enalapril is effective in reducing hepatic ischemia/reperfusion damage as assessed by the leukocyte-endothelium interaction using in vivo microscopy and postreperfusion bile production.
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PMID:Impact of enalapril on microvascular perfusion and leukocyte adherence in a model of rat liver transplantation assessed by in vivo microscopy. 895

Endothelial driving factors pathophysiologically affect the regulation of coronary circulation. To investigate the regulation of vascular function by endothelium-derived relaxing factor (EDRF) and endothelial cells, endothelium-dependent relaxation impairment was studied in acute ischemia-reperfusion injury in large coronary artery and coronary microvasculature. EDRF (NO) production and release were inhibited due to ischemia-reperfusion injury to the endothelium of large coronary arteries. There was an increased sensitivity selective to ET-1 in large coronary arteries exposed to ischemia and reperfusion. Reduced endothelium-dependent relaxation and augmented ET-1 sensitivity in large coronary arteries suggest the existence of spasmogeneity in reperfused blood vessels. Ischemia and reperfusion also brought about various morphological and functional changes in the reperfused coronary microvasculature. Edema of perivascular interstitium and endothelial cells was the main observation and caused a decrease in the ability of the microvascular bed to dilate because of extravascular compression. To examine the long-term suppression of NO synthesis accompanying endothelial dysfunction, the long-term reactions of coronary arteries and myocardium due to chronic inhibition of NO synthesis by continuously infused L-NAME was investigated. Endothelial cell impairment, proliferation and disarrangement of medial smooth muscle cells, microvascular injury due to platelet thrombi and increased perivascular fibrous tissue were found in rat coronary arteries. Myocardial fibrosis due to coronary microvascular injury was observed. These changes in coronary arterial and myocardial structure were suppressed by ACE inhibitors. Therefore, ACE inhibitors are useful in the treatment of coronary microvascular impairments.
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PMID:Regulation and failure of coronary circulation. 897 73

Recently we have shown that ACE inhibitors and platelet activating factor antagonists inhibit iron-dependent lipid peroxidation in murine ventricular membranes and possess beneficial effects on ischemia and ischemia reperfusion-induced myocardial injury, which has been ascribed to their capacity to scavenge or impair oxygen free radical generation. In the present study we investigated the effects of beta-adrenoceptor blockers and calcium antagonists on iron-dependent lipid peroxidation (LPO) in murine ventricular membranes and compared them with the lazaroid U-74500A, a potent antioxidant. Fe(2+)-vitamin C induced LPO in a concentration- and time-dependent manner, measured as thiobarbituric acid reactive substances (TBARS) formation. Pretreatment of ventricular membranes with gallopamil, verapamil, propranolol and metaprolol at concentrations of 5 microM and higher inhibited Fe(2+)-vitamin C-induced LPO in a concentration-dependent manner with IC50 values of 192.8-208.3 microM; however, they were less potent than U-74500A (IC50 6.8 microM). In contrast, atenolol, timolol, diltiazem and nifedipine inhibited LPO at very high concentrations with IC50 values of 864.5-971.5 microM. Inhibition of LPO may not be due to the drugs' classical pharmacological actions, but rather to their characteristic chemical structures or physicochemical interactions with biological membranes. In view of the pathological importance of LPO in cardiac ischemic injury, inhibition of LPO by gallopamil, verapamil, propranolol and metaprolol may provide additional cardioprotective activity and thus reinforces their beneficial effects in the treatment of ischemic heart disease.
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PMID:Comparative antioxidant effects of beta-adrenoceptor blockers, calcium antagonists and U-74500A against iron-dependent lipid peroxidation in murine ventricular microsomal membranes. 901 Aug 29

The attenuation of myocardial stunning by the ACE inhibitor ramiprilat is prevented by cyclooxygenase inhibition with indomethacin. In the clinical setting of ischemia/reperfusion however, the cyclooxygenase inhibitor aspirin is widely used to prevent platelet aggregation. The present study therefore investigated whether aspirin in dosages sufficient to inhibit platelet aggregation interferes with the attenuation of myocardial stunning by ramiprilat. Fifteen dogs received either 1 mg/(kg.day) (group I, n = 7) or 10 mg/(kg.day) (group II, n = 8) aspirin orally for 1 week. Both dosages of aspirin inhibited ADP-induced platelet aggregation. The dogs were then anesthetized thoracotomized and subjected to 15 min LCx-occlusion and 4 h reperfusion. Before LCx-occlusion, groups I and II received ramiprilat (20 micrograms/kg, i.v.). Systemic hemodynamics, posterior myocardial blood flow (PMBF, colored microspheres) and wall thickening (PWT, sonomicrometry) of these groups were measured and data compared to placebo-controls (group III, n = 11) and dogs receiving only ramiprilat before LCx-occlusion (group IV, n = 11). Four dogs received 10 mg/(kg.day) aspirin without ramiprilat (group V). Mean aortic pressure was kept constant by an intra-aortic balloon, and heart rate did not change. PMBF was not different between the five groups. Under control conditions and during myocardial ischemia PWT was also not different. At 4 h reperfusion PWT was still depressed in group III (-5 +/- 20% of control) and group V (-23 +/- 6%) whereas PWT recovered to the same extent in groups I (46 +/- 23%), II (50 +/- 15%) and IV (58 +/- 18%) (all P < 0.05 v groups III and V). The attenuation of myocardial stunning by the ACE inhibitor ramiprilat is not prevented by aspirin in dosages which are nevertheless sufficient to inhibit platelet aggregation.
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PMID:Aspirin does not prevent the attenuation of myocardial stunning by the ACE inhibitor ramiprilat. 901 43

Tissue edema is a facet of ischemia/reperfusion injury in many organs, polymorphonuclear leukocytes (PMN) presumably playing a contributory role. We studied the intracoronary adhesion of PMN and its effect on vascular permeability during reperfusion in isolated guinea-pig hearts. After a global ischemia of 15 min duration. PMN (10(7)) were infused into the coronary system during the first minute of reperfusion. PMN adhesion was measured as difference of applied PMN and those recovered in the effluent perfusate. Coronary permeability was assessed by measuring the rate of transudate formation (TF) on the epicardial surface, before as well as 5, 15 and 30 min after ischemia. Experiments were also performed in the presence of the NO-synthase inhibitor nitro-L-arginine (10 microM) and the ACE-inhibitor ramiprilat (2 microM), the latter known to enhance endogenous nitric oxide formation. Furthermore, the radical scavenger uric acid (0.5 mM) was applied either before and during ischemia or starting after PMN application. Ischemia/reperfusion increased coronary PMN adherence from 23 +/- 1% (basal) to 33 +/- 2%. Whereas ischemia alone did not influence TF (about 100 microliters/min during reperfusion), postischemic PMN infusion led to progressive TF. With nitro-L-arginine, PMN adhesion rose to 45 +/- 3%; TF increased to 212 +/- 30 microliters/min. In contrast, ramiprilat caused post-ischemic adhesion and TF to decline to basal values. In the presence of uric acid (UA) PMN adhesion declined to 26 +/- 2%, however, the subsequent increase in TF after withdrawal of UA was not markedly attenuated. On the other hand, infusion of UA after application of PMN caused a significant decrease of TF. The extracellular antioxidants SOD/catalase were without effect. As shown using luminol enhanced chemiluminescence. No was able to scavenge oxygen free radicals released by activated PMN. These findings indicate that enhanced PMN adhesion in reperfusion leads to an increase in coronary permeability. Scavenging of oxygen free radicals with NO or UA appears to mitigate both, postischemic PMN adhesion and PMN-induced vascular injury, even after adhesion.
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PMID:Nitric oxide mitigates leukocyte adhesion and vascular leak after myocardial ischemia. 901 47

There is a subgroup of patients with coronary artery disease who are refractory to the therapeutical methods so far applied. We report on 128 patients who fulfill this definition and have therefore undergone pure transmyocardial laser revascularisation (TMLR) or transmyocardial laser revascularisation in combination with coronary bypass surgery at our institution. The patients can be characterized by a long history of coronary artery disease with multiple revascularizing procedures, e.g. bypass surgery or percutaneous transluminal coronary angioplasty (PTCA), pronounced symptoms of coronary artery disease and chronic heart failure in the presence of markedly reduced left ventricular ejection fractions and intense antiischemic medical therapy. The patients were 62.2 +/- 9.8 (SD) years of age, in 89.9% of them at least one bypass operation and in 44.5% up to more than three percutaneous transluminal coronary angioplasties (PTCAs) had been performed prior to TMLR. There was a history of myocardial infarction in 90.7% of patients and 89.8% were in the Canadian Cardiovascular Society (CCS) classes III or IV and 94.5% of them were in the NYHA classes III or IV. The left ventricular ejection fraction was 49.5 +/- 16.4% and all of the patients were under intense antiischemic medical treatment which included nitrates or molsidomine in 96.9%, beta blockers in 53.1%, angiotensin converting enzyme inhibitors (ACE inhibitors) in 44.5%, digitalis in 22.7% and diuretics in 52.3% of patients. The preoperative data on myocardial viability, inducible ischemia and coronary morphology provided important clinical information for the decision, which revascularizing method would be the most appropriate for each vessel or myocardial region. This had to be weighed against the patient's operative risk, which is predominantly determined by the left ventricular ejection fraction, the arteriosclerotic involvement of the remaining vascular system and concomitant diseases, particularly of pulmonary origin.
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PMID:Patients' profiles in end stage coronary artery disease. Indications for treatment with transmyocardial laser revascularisation. 928 37

Cardiac dysrhythmias are common during anesthesia and surgery. An important precipitating factor of clinically relevant arrhythmias is the introoperative use of epinephrine. Bradykinin acts as an endogenous cardioprotective substance because it suppresses ventricular dysrhythmias induced by ischemia. In this study, we investigated whether bradykinin has a protective effect, preventing the development of dysrhythmias after epinephrine infusion in rats. Because kinins are potent stimulators of the release of nitric oxide and prostaglandins from the endothelium, we investigated whether the protective effect of bradykinin is mediated by these 2 autacoids. Male Sprague-Dawley rats anesthetized with sodium pentobarbital had catheters placed into a carotid artery and both jugular veins. Arterial blood pressure and lead II of the electrocardiogram (ECG) were continuously monitored and recorded. After a steady state was achieved, 1 mg/kg enalapril, an inhibitor of angiotensin I-converting enzyme/kininase II, was given intravenously to all groups except the one treated with losartan. Bradykinin was infused at the initial rate of 0.5 microg/kg per min. Cardiac arrhythmia was induced with 7.5 microg/kg epinephrine intravenously. Dysrhythmia was assessed by counting the number of premature ventricular contractions (PVCs), runs of ventricular tachycardia (V Tach), and missing beats during the first minute after epinephrine. In untreated, control rats, epinephrine caused 10.8 +/- 2.7 PVCs, 0.8 +/- 0.2 runs of V tach, and 11.6 +/- 7.4 missing beats/min. In rats pretreated with bradykinin, the same dose of epinephrine elicited 1.2 +/- 0.5 PVCs, no runs of V tach, and 0.4 +/- 0.4 missing beats/min. This beneficial effect of bradykinin was partially reversed by N-nitro-L-arginine methyl ester (L-NAME) or indomethacin, and completely by L-NAME plus indomethacin or icatibant, but it was not affected by des-Arg9[Leu8]-bradykinin. We conclude that bradykinin, acting on the B2 receptor, attenuates epinephrine-induced dysrhythmia via a mechanism that involves the release of NO and prostaglandins. Although the mechanism is not clear, NO and prostaglandins may prevent epinephrine-induced dysrhythmia and protect the myocardium via a direct action on cardiac neurons.
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PMID:Attenuation of epinephrine-induced dysrhythmias by bradykinin: role of nitric oxide and prostaglandins. 929 70

The variable prognosis after myocardial infarction necessitates an individual tailoring of follow-up treatment. Therapeutic decisions must be based on a complete risk stratification including assessment of persisting ischemia, left ventricular function, rhythmic instability and cardiovascular risk factor profile. High risk patients (prognostic indication) as well as symptomatic patients (symptomatic indication) should be referred for coronary angiography to assess the need for revascularisation procedures (PTCA, CABG). The individual risk profile also defines drug therapy for secondary prevention (not more than 3-4 drugs): anti-platelet agents or anticoagulation in every patient; beta blockers in all but the lowest risk group; ACE-inhibitors in heart failure or asymptomatic, substantial left ventricular dysfunction; liberal use of cholesterol-reducing drugs. Life style alterations should be encouraged in almost every patient. Information about the necessary measures to be taken upon occurrence of angina at rest or other cardiac symptoms must be repeatedly given to all patients.
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PMID:[After care of acute myocardial infarct: what are the 4 most important points?]. 932 21

The antiarrhythmic effects of captopril, a sulphydryl-containing angiotensin converting enzyme (ACE) inhibitor, were compared with those of the nonsulphydryl-containing ACE inhibitor lisinopril and the sulphydryl-containing agent glutathione in an in vivo rat model of coronary artery ligation. To produce arrhythmia, the left main coronary artery was occluded for 7 min, followed by 7 min of reperfusion. Captopril (3 mg kg-1) and lisinopril (0.1, 0.3 or 1 mg kg-1) caused marked decreases in mean arterial blood pressure (BP) and heart rate, whereas glutathione (5 mg kg-1) had no effect on them. The incidence of ventricular tachycardia (VT) on ischemia and reperfusion was significantly reduced by captopril and lisinopril. Captopril and 1 mg kg-1 lisinopril also significantly decreased the number of VEB during occlusion and the duration of VT on reperfusion, respectively. These drugs also attenuated the incidence of reversible ventricular fibrillation (VF) and the number of ventricular ectopic beats (VEB) during reperfusion. However, glutathione only reduced the incidence of VT on reperfusion, significantly. These results suggest that, in this experimental model, ACE inhibitors limit the arrhythmias following ischemia-reperfusion and free radical scavenging action of these drugs does not have a major contributory role in their protective effect.
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PMID:Protective effect of ACE inhibitors on ischemia-reperfusion-induced arrhythmias in rats: is this effect related to the free radical scavenging action of these drugs? 941 67

Cardiovascular complications are the most common causes of morbidity and mortality in diabetic patients. Coronary atherosclerosis is enhanced in diabetics, whereas myocardial infarction represents 20% of deaths of diabetic subjects. Furthermore, re-infarction and heart failure are more common in the diabetics. Diabetic cardiomyopathy is characterized by an early diastolic dysfunction and a later systolic one, with intracellular retention of calcium and sodium and loss of potassium. In addition, diabetes mellitus accelerates the development of left ventricular hypertrophy in hypertensive patients and increases cardiovascular mortality and morbidity. Treating the cardiovascular problems in diabetics must be undertaken with caution. Special consideration must be given with respect to the ionic and metabolic changes associated with diabetes. For example, although ACE inhibitors and calcium channel blockers are suitable agents, potassium channel openers cause myocardial preconditioning and decrease the infarct size in animal models, but they inhibit the insulin release after glucose administration in healthy subjects. Furthermore, potassium channel blockers abolish myocardial preconditioning and increase infarct size in animal models, but they protect the heart from the fatal arrhythmias induced by ischemia and reperfusion which may be important in diabetes. For example, diabetic peripheral neuropathy usually presents with silent ischemia and infarction. Mechanistically, parasympathetic cardiac nerve dysfunction, expressed as increased resting heart rate and decreased respiratory variation in heart rate, is more frequent than the sympathetic cardiac nerve dysfunction expressed as a decrease in the heart rate rise during standing.
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PMID:Diabetes mellitus and cardiac function. 954 31


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