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)

Restoration of coronary blood flow in the ischemic myocardium is absolutely needed to prevent irreversible cellular damage but on the other hand may have potentially hazardous consequences. Since thrombolysis during myocardial infarction is designed to salvage a maximal number of myocardial cells threatened by ischemia, a concommitant intervention which reduces cellular damage due to reperfusion will improve the net result of such procedure. The adjunctive use of ACE-inhibitors with thrombolytic therapy early during acute myocardial infarction offers theoretic advantages. This article summarizes the results indicating that ACE-inhibitors do play an important role in cardioprotection in the acute phase of myocardial ischemia followed by reperfusion. Probably, their effect on bradykinin breakdown is at least partly responsible for this effect.
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PMID:Early ACE-inhibition in myocardial infarction. Possible role of bradykinin. 146 86

In experimental ischemic dog heart with coronary-constriction, no increase of coronary blood flow, Max dP/dt or MVO2 with no change of kinin in arterial blood were exhibited. Following sympathetic nerve stimulation, remarkable increases of kinin in coronary sinus blood were observed with a significant elevation of left ventricular end-diastolic pressure and an augmented production of lactate from the heart as well as an ischemic change of ECG-ST. Infusion of kinin into the left main coronary artery resulted in no change in the mean systemic blood pressure, coronary blood flow, coronary vascular resistance, cardiac function, myocardial metabolism or ECG-ST in the control and coronary-constricted groups. These data suggest that kinin was released significantly from the ischemic heart, however, such a level of kinin has no significant effect on coronary circulation or myocardial metabolism. In ischemia-reperfusion rabbit hearts, no significant influence of the ACE inhibitors, captopril and ramiprilat, were observed. Species differences may be responsible for the beneficial role of ACE inhibitors in the limitation of infarct size in the dog hearts, possessing collateral flow, that are not seen in the rabbit heart with poor collateral flow.
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PMID:Activation of kinins on myocardial ischemia. 146 87

Left ventricular hypertrophy (LVH) constitutes a powerful independent risk factor in hypertensive heart disease. Although initially the wall stress, i.e., left ventricular afterload, remains normal, the coronary reserve is diminished due to disturbances in the microcirculation. This is also shown in the commonly present silent ischemia episodes in Holter monitoring. LVH also causes ventricular dilation and heart failure. Apart from systolic wall stress LVH is modulated by the trophic effects of the sympathetic nervous system and angiotensin II and genetic factors. Long-term antihypertensive treatment must therefore focus on regression of both LVH and the microvascular abnormalities. A step approach for the treatment of the LVH has been recommended on the basis of the experience of this working group with calcium antagonists and ACE inhibitors, whereas the place of beta-blockers is as yet unclear. Preliminary data indicate that coronary flow rescue can also be improved after chronic antihypertensive treatment.
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PMID:Therapeutic effect on left ventricular hypertrophy by different antihypertensive drugs. 153 67

Patients with hypertension requiring therapy frequently present with concurrent peripheral vascular disease (PVD). This situation must be taken into account for an optimum antihypertensive treatment. In general, in patients with PVD only a cautious and gradual lowering of the blood pressure is recommended, since the decrease in poststenotic perfusion pressure may accentuate the symptoms of occlusive disease. In intermittent claudication--the most frequent manifestation of occlusive disease beta--receptor blockers today are no longer considered to be contraindicated. In the presence of critical ischemia of the legs (pain at rest and/or necroses) beta blockers should only be given with extreme caution. The agents of choice are calcium antagonists, ACE -inhibitors as well as alpha blockers and some newer vasodilating substances (e.g. Carvedilol). Conventional diuretics show disadvantages. An slightly elevated blood pressure in critical leg ischemia helps to improve the poststenotic perfusion of the affected limb. Antihypertensive treatment should not be instituted in patients whose systolic blood pressure is lower than 160 mmHg.
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PMID:[Antihypertensive therapy in arterial occlusive disease]. 168 38

Recent studies in animal models suggest that glomerular capillary hyperperfusion and hypertension, rather than ischemia, cause renal injury. Interventions that control glomerular capillary hypertension may protect against progressive injury, even in the presence of continued systemic hypertension. In the absence of systemic hypertension, diabetes mellitus is a prominent clinical example of glomerular hypertension. Animal studies have shown that glomerular hemodynamic abnormalities, especially elevations in glomerular pressure, play an important role in the pathogenesis of diabetic glomerulopathy. A number of clinical observations suggest that angiotensin converting enzyme (ACE) inhibitors may delay the progression of diabetic nephropathy by their effects on renal hemodynamics. In experimental animals, comparisons between calcium channel blockers and ACE inhibitors have shown the latter to be more effective in protecting the kidneys. Preliminary clinical studies indicate that ACE inhibitors may have advantages in preserving renal function in hypertensive and diabetic patients with renal failure.
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PMID:Renal effects of converting enzyme inhibitors in hypertension and diabetes. 169 12

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.
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PMID:Local inhibition of bradykinin degradation in ischemic hearts. 169 70

Changes in left ventricular remodeling due to antihypertensive therapy have been demonstrated in experimental animal studies although no quantitative relationship has been shown between correction of blood pressure and regression of myocardial mass. As regards the qualitative aspects of regression, only the ACE inhibitors have been shown to prevent the development and induce regression of the excess collagen content of the myocardium submitted to chronic pressure overload. The problems posed by remodeling in clinical practice are more complex: should regression of myocardial mass itself be the therapeutic objective in the absence of a practical method of analysing the interstitial factor of hypertensive disease or should we concentrate on the satellite problems of hypertrophy which are correction of ischemia, left ventricular filling abnormalities and arrhythmias. For each of these clinical problems, the benefits attributed to changes in remodeling, though probable, are to a large degree hypothetical. The benefits offered by these drugs which reduce ventricular hypertrophy are, however, considerable.
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PMID:[Left ventricular remodeling and hypertension. Course with antihypertensive therapy]. 183 22

The purpose of this investigation was to study the effect of an angiotensin converting enzyme inhibitor (enalaprilat) on the morphologic manifestations of experimentally induced necrotizing tracheobronchitis (NTB). Twenty piglets were anesthetized before saline lung lavage. High frequency flow interrupter (HFFI) ventilation was used with a strategy known to produce NTB. Animals were randomly assigned to receive IV enalaprilat 0.1 mg/kg (ENP-Hi), enalaprilat 0.01 mg/kg (ENP-Lo), or saline (C). After 8 hours of ventilation, the piglets were sacrificed. Total airway injury scores (mean +/- S.D.) were 1.2 +/- 0.7 for ENP-Hi, 0.2 +/- 0.2 for ENP-Lo, and 21.3 +/- 16 for group C. Enalaprilat minimizes NTB lesions in neonatal piglets exposed to high frequency oscillatory ventilation. Although the origin of NTB is multifactorial, airway mucosa ischemia may play an important role. Enalaprilat may compensate for the reduction of mucosal blood flow by limiting formation of angiotensin II and/or preventing degradation of bradykinin.
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PMID:Necrotizing tracheobronchitis (NTB) following high frequency ventilation: role of an angiotensin converting enzyme inhibitor. 184 39

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)
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PMID:[ACE inhibition: mechanisms of "cardioprotection" in acute myocardial ischemia]. 186 30

Acute myocardial ischemia results from an increased cardiac workload in presence of a critical coronary stenosis (demand ischemia), coronary occlusion (supply ischemia) or a combination of both. It is complicated by cardiac arrhythmias and deterioration of function of ischemic myocardium and results in an increased load and dilatation of non-ischemic myocardium. Cardiac protection in acute myocardial ischemia can be related to preservation of coronary blood flow, function of ischemic and non-ischemic myocardium or prevention of cardiac arrhythmias. In control animals and humans, ACE-inhibitors have no major effect on coronary blood flow. Myocardial ischemia raises plasma-renin-activity, angiotensin I-conversion by passage through coronary circulation, and plasma-angiotensin-II-concentrations. ACE-inhibitors and angiotensin-II-receptor blockers increase coronary blood flow during myocardial ischemia. Other mechanisms (bradykinin potentiation) may be involved. We found a potentiation of the coronary dilatory effect of the neuropeptide neurotensin (which is probably mediated by prostaglandins) by ACE-inhibitor. ACE-inhibitor may delay infarct development in animal experiments and improve function of ischemic myocardium. The importance of early dilatation of non-ischemic myocardium is unknown and it is unclear whether it may be prevented by an ACE-inhibitor as was shown for late dilatation. Studies on the effect of ACE-inhibitors in exercise-induced angina pectoris are controversial. An antiischemic and coronary dilatory effect has been shown by invasive studies in patients. A preliminary study in unstable angina pectoris was positive. Beneficial hemodynamic and antiarrhythmic effects (as well as excessive hypotension, however) have been shown in patients with acute myocardial infarction.
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PMID:[Possibilities of ACE inhibitor therapy in acute myocardial ischemia]. 186 31


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