Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma renin activity (PRA) stimulated by upright posture was measured, in 300 men aged 45-64 years, by a radio-immunoassay of angiotensin I. The subjucts examined were divided into six groups, comparable in mean age, each containing 50 subjects: group 1, normotensives without manifest atherosclerosis; group 2, normotensives with angina pectoris definite; group 3, normotensives with a history of a transmural myocardial infarction; groups 4 to 6, patients with benign essential hypertension, without manifest atherosclerosis in group 4, with angina pectoris in group 5 and with a history of myocardial infarction in group 6. Significant differences in mean PRA were found between corresponding groups of hypertensives and normotensives, the values in hypertensives being lower. The precentage of low renin values was higher in hypertensives with ischaemic heart disease than in other groups. An analysis of 3-year cardiovascular mortality revealed no significant difference in mortality due to ischaemic heart disease between high-renin and low renin sub-groups.
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PMID:Plasma renin activity in men with relation to the presence of ischaemic heart disease. 85 14

Among the interventions designed to limit postischemic oxidative injury, those that enhance the myocardial content of thiol groups are attractive because thiols are powerful antioxidant. Indeed, part of the protection afforded by the angiotensin-converting enzyme (ACE) inhibitor captopril in regional myocardial ischemia is attributed to its thiol group. This study assesses the effects of captopril in a surgically relevant model of global ischemic arrest. Thirty rats were implanted subcutaneously (s.c.) with osmotic pumps that allowed continuous delivery of captopril (total dose 75 mg), enalapril (a nonthiol-containing ACE inhibitor, total dose 7.5 mg) or saline in 48 h. Drug concentrations were equipotent in their effect on angiotensin I (ANGI) pressor response. Hearts were then excised, perfused under isovolumic conditions, and subjected to 90-min cardioplegic arrest at 30 degrees C followed by 1-h reperfusion. Pre- and postischemic coronary flows were significantly higher to a similar extent in the two drug-pretreated groups than in controls. However, captopril-pretreated hearts had the best recovery of contractility (dP/dtmax; 3,590 +/- 74 versus 2915 +/- 64 mm Hg s-1 in the enalapril group, p less than 0.001), and diastolic pressure (13.7 +/- 0.9 mm Hg vs. 20.0 +/- 1.6 mm Hg in the enalapril group, p less than 0.05). We conclude that pretreatment with ACE inhibitors improves myocardial recovery after cardioplegic arrest and that captopril is more effective than enalapril. The additional protection afforded by captopril was not flow mediated, suggesting that the cardioprotective effects of this drug not only involve an ACE inhibition-dependent coronary vasodilation but could be related to a thiol-dependent limitation of oxidative injury.
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PMID:Pretreatment with captopril improves myocardial recovery after cardioplegic arrest. 137 21

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

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

We used the technique of high-performance liquid chromatography combined with radioimmunoassay to establish the profile of angiotensin peptides in the periphery and across the circulation of the dog's heart. Data were obtained before and after blockade of angiotensin converting enzyme, and after acute myocardial ischemia produced by occlusion of the left anterior descending coronary artery. Baseline values of plasma renin activity and immunoreactive angiotensin II were higher in the aortic root than in the coronary sinus but concentrations of angiotensin I and angiotensin-(1-7) were similar. In untreated animals, coronary occlusion produced significant increases in renin activity and arterial and venous levels of angiotensin I and angiotensin II. Inhibition of converting enzyme with benazeprilat (CGS-14,831) increased baseline circulating levels of angiotensin I, whereas angiotensin II and its carboxyl terminal fragments were reduced markedly. Baseline plasma levels of angiotensin-(1-7) and its fragments did not change. Myocardial ischemia in benazeprilat-treated dogs increased plasma renin activity and circulating levels of angiotensin I. Concentrations of angiotensin II and angiotensin-(1-7) did not change either in peripheral blood or across the coronary circulation. These results indicate that angiotensin peptides can be formed endogenously by enzymatic pathways alternate to converting enzyme. Furthermore, these data provide the basis for a further understanding of the role of the renin-angiotensin system after myocardial ischemia.
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PMID:The renin-angiotensin system during acute myocardial ischemia in dogs. 240 54

To investigate the influence of local cardiac converting enzyme (CE) inhibition on the effects of angiotensin I (ANG I), ANG II, and bradykinin (BK), experiments were performed in ischemic isolated perfused working rat hearts. Acute regional myocardial ischemia was induced by 15 min occlusion of the left coronary artery followed by reperfusion. In ischemic isolated rat hearts, perfusion with ramiprilat (100 ng/ml, 2.58 x 10(-7) mol/l), the active moiety of the CE inhibitor ramipril, after coronary occlusion protected against ventricular fibrillation that invariably occurred in untreated control hearts in the reperfusion period. Addition of ANG I and ANG II to the perfusate enhanced, whereas BK reduced postischemic reperfusion arrhythmias, which were almost abolished in the hearts from ramipril (1 mg/kg p.o.) pretreated rats. Perfusion with ANG I and ANG II reduced cardiac function and coronary flow, increased the activities of lactate dehydrogenase and creatine kinase in the perfusate, and decreased high-energy-rich phosphates and glycogen in the myocardium. In contrast, BK reduced the enzymatic activities in the perfusate and improved the metabolic parameters in the myocardium. In hearts from ramipril pretreated animals, the ANG I effects were abolished, whereas the ANG II actions remained unchanged. The results of these experiments are consistent with the hypothesis that the beneficial effects of CE inhibitors on ventricular arrhythmias, cardiac function, and metabolism are due to local interference with CE in the coronary vascular wall or heart tissue and subsequent reduction of local ANG II generation and BK degradation.
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PMID:Influence of local converting enzyme inhibition on angiotensin and bradykinin effects in ischemic rat hearts. 248 67

Previous attempts to define the etiology of coronary arterial spasm have been focused on mechanisms such as autonomic nervous dysfunction and/or enhanced platelet activation. In the present study, humoral regulation was investigated in patients with vasospastic angina and scintigraphically documented transient myocardial perfusion abnormalities after a peripheral cold pressor test. Serial changes in angiotensin II, epi- and norepinephrine as well as thromboxane B2 (the stable derivate of thromboxane A2), and malondialdehyde were determined at baseline (I), immediately after 5 minutes cold water hand immersion (II), and following 10 minutes recovery (III). Angiotensin II and epinephrine remained unchanged during observation (I vs II, II vs III: P = NS). Norepinephrine was elevated after cold (I vs II: P less than 0.001) and normalized after 10 minutes (I vs III: P = ns). Thromboxane B2 and malondialdehyde increased continuously (I vs III: P less than 0.05 and I vs III: P less than 0.002, respectively). Further radiothin-layer chromatography results indicate an activation of platelet function during myocardial ischemia. Our results do not establish a cause-effect relationship but, together with other evidence, they may suggest that thromboxane A2 is unlikely to be the cause of spasm. It might, however, play an important role in the maintenance of vasoconstriction.
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PMID:Humoral regulation during cold-induced coronary arterial spasm. 280 8

The protective effect of angiotensin-converting enzyme inhibitors (ACEI) on myocardial ischemia and reperfusion damage was estimated in rat hearts, both in vivo and in vitro. Enalapril 2.5 mg/kg ip pretreatment at 24 and 5 h before coronary occlusion, significantly blunted the rise of CPK (445 +/- 151 vs 649 +/- 244 mu/ml, P less than 0.05) and improved electrocardiogram (ECG) 8 h after coronary occlusion. In global ischemia and reperfusion ex vivo, enalapril improved contractility (0.9 +/- 0.2 vs 0.3 +/- 0.3 g, P less than 0.05) and coronary flow (15.6 +/- 3.3 vs 11.9 +/- 3.1 ml/min/g, P less than 0.05), shortened significantly the duration of reperfusion arrhythmia (3.1 +/- 2.7 vs 9.7 +/- 8.1 min, P less than 0.05). In Langendorffs heart, captopril remarkably preserved force of contraction (2.1 +/- 0.4 vs 1.4 +/- 0.4 g, P less than 0.01) and coronary flow (2.7 +/- 0.5 vs 3.6 +/- 0.9 ml/min/g, P less than 0.05) in segmental infarction deteriorated by angiotensin I. Captopril 10(-5) M infusion reduced the release of CPK (435 +/- 112 vs 640 +/- 123 mu/min coronary flow, P less than 0.05). This action was almost completely abolished by pretreating and infusing with indomethacin. As a positive control, prostacyclin 5 X 10(-7) M infusion further reduced the release of CPK to 330 +/- 77 mu/min. It is concluded that angiotensin-converting enzyme inhibitor can protect both myocardial ischemia and reperfusion damage in rat hearts. The mechanism of protection was ascribed to reduced production of angiotensin II by ACE inhibition and increased prostacyclin release in the myocardium.
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PMID:Protective effects of captopril and enalapril on myocardial ischemia and reperfusion damage of rat. 282 45

The emerging recognition of the existence and potential biological significance of local tissue renin-angiotensin systems in a number of organs has fostered interest in a possible intrinsic cardiac renin-angiotensin system. Evidence for such a system was first provided by biochemical measurements of components of the renin-angiotensin system in cardiac tissue. It has recently been demonstrated that the genes coding for renin and angiotensinogen are expressed in all regions of the heart, an essential prerequisite for the postulated intracardiac biosynthesis of these proteins. Moreover, we have shown the presence of a functional and physiologically active pathway for the conversion of angiotensin I to angiotensin II in the beating mammalian heart. This conversion appears to be catalyzed by a specific cardiac converting enzyme that is susceptible to systemically administered converting-enzyme inhibitors. Evidence for the physiologic importance of the cardiac renin-angiotensin system comes from experimental data as well as indirect clinical evidence. The potent coronary vasoconstrictor properties of angiotensin II underscore its possible significance in myocardial ischemia and ischemic heart disease, in particular when viewed in the context of selective local activation. The long-known positive inotropic effects of angiotensin II are based on its direct myotropic properties and on its facilitatory effects on sympathetic neurotransmission and may be of added significance in metabolically compromised states. We have recently demonstrated that locally generated angiotensin may be a dominant etiologic factor in the pathogenesis of reperfusion arrhythmias. In addition, we have found experimental evidence for a deleterious effect of angiotensin II on myocardial metabolism in the setting of regional myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intracardiac generation of angiotensin and its physiologic role. 328 43

Enalapril, a potent angiotensin converting enzyme inhibitor, effectively blocked the constrictor actions of angiotensin I in isolated perfused cat coronary arteries. Enalapril, at concentrations of 25 to 100 micrograms/ml, inhibited angiotensin I by 65 to 80%. Moreover, enalapril at 100 to 200 micrograms/ml, markedly antagonized the coronary vasoconstrictor effects of angiotensin II. At 150 micrograms/ml, enalapril blocked the angiotensin II response by 80 +/- 5%, and at 200 micrograms/ml, it was blocked by 95 +/- 4%. Enalaprilic acid at 0.5 to 1.0 microgram/ml also blocked the angiotensin II response by 94 +/- 5%. Captopril, up to 250 micrograms/ml, failed to significantly antagonize angiotensin II, although it readily blocked angiotensin I in this preparation. The duration of this angiotensin II blockade lasted about 60-90 min. This angiotensin II antagonism may help explain the beneficial effects of enalapril in situations such as acute myocardial ischemia.
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PMID:Coronary vascular actions of the converting enzyme inhibitor, enalapril. 632 Feb 8


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