Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002962 (angina)
 21,142 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In isolated perfused rabbit hearts, bradykinin produced a concentration-dependent decrease in coronary resistance directly associated with biosynthesis and release of prostaglandin-E-like substance. An inhibitor of bradykinin destruction (the nonapeptide SQ-20881) markedly enhanced both the coronary vasodilation and release of prostaglandin-E-like substance produced by cardiac injection of bradykinin. Indomethacin inhibited both the myocardial prostaglandin biosynthesis and the decrease in coronary resistance induced by bradykinin. The demonstration that bradykinin is a potent stimulator of prostaglandin biosynthesis in the heart has implications as to the cause of the afferent cardiovascular reflexes and pain in myocardial infarction and angina pectoris.
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PMID:Mechanism and modification of bradykinin-induced coronary vasodilation. 105 12

There is considerable evidence that on the anterior surface of the heart (which is usually supplied by the left anterior descending and the proximal part of the left circumflex coronary arteries), sympathetic efferent reflexes characterized by tachycardia and/or hypertension predominate following experimental or pathological perturbations. These cardiovascular reflexes are accompanied by an increase in presumed nociceptive afferent traffic and, in pathological condition, by pain. In these experiments, there is generally no effect of vagotomy on afferent nerve traffic, and lower cervical and upper thoracic sympathectomies help provide relief from angina. On the other hand, experimental or pathological perturbations involving the inferior-posterior surface of the heart (supplied by the right and distal parts of the left circumflex coronary arteries), are characterized by vagal efferent reflexes, resulting in bradycardia and/or hypotension. These reflexes are accompanied by an increase in vagal afferent nerve traffic and, in pathological conditions, by pain. In these experiments, vagotomy generally abolishes such cardiovascular reflexes, and lower cervical and upper thoracic sympathectomies are not effective in the relief from angina. Although cardiac sympathetic afferents are unquestionably involved in the central transmission of nociceptive information from the heart, it is also likely that there is a contributing role from the vagus in cardiac pain. It is important experimentally to understand the natural stimulus that gives rise to angina. In the clinical situation, a decrease in coronary blood flow or an increase in the metabolic demands of the myocardium due to increased work are obvious precipitating factors which lead to myocardial ischemia. In the experimental situation, occlusion of the coronary arteries is often used as a stimulus which mimics myocardial ischemia. As people who frequently experience angina have varying degrees of coronary artery disease, it is difficult to accept that the state of the coronary arteries of the normal experimental animal bear any resemblance to the state of the coronary arteries under pathological conditions. That is, the gain of homeostatic reflexes, the basal concentrations of neuroactive substances in the plasma, the myocardium and the afferent terminals, the excitability of the afferents, access of chemical mediators (e.g. bradykinin, 5-HT, adenosine, histamine, prostaglandins, potassium, lactate), to afferents, and the overall function of the animal are all significantly different. We have no idea how control mechanisms have been altered in the person with severe coronary artery disease compared to the normal patient or the "normal" experimental animal.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A critical review of the afferent pathways and the potential chemical mediators involved in cardiac pain. 135 Dec 70

The regulation of coronary hemodynamics is a complex process. One important factor that interferes with the regulation of coronary tone is the pathophysiological state of the vessels: stimuli that in normal vessels provoke no or only a slight vasoconstriction may cause a severe vasoconstriction in diseased vessels. This effect is related to the function of the endothelium and its ability to produce nitric oxide and prostaglandins. The presence of a local renin-angiotensin system implies the possibility of influencing the coronary flow via interference with this local system. Therefore, it is interesting to determine the effects of converting enzyme inhibitors on coronary flow. In animal experiments, a bradykinin-dependent coronary vasodilation by angiotensin-converting enzyme (ACE) inhibitors is suggested. However, reports on the effect of converting enzyme inhibitors in patients with angina pectoris are not consistent. Some authors found an increase in coronary flow and others found no change or a decrease. The importance of the activation of the renin-angiotensin system is discussed. Moreover, it is shown that captopril reduces sympathetic-mediated coronary vasoconstriction during the cold pressor test and that captopril enhances the parasympathetic-mediated bradycardia during the diving response. In conclusion, the effects of converting enzyme inhibitors on coronary flow is an interesting but not fully understood topic. Therefore, the multifactorial mechanism of action of converting enzyme inhibitors deserves further investigation. There are probably subgroups of anginal patients who may benefit from converting enzyme inhibitor therapy. These subgroups have to be defined. Especially, the finding that a converting enzyme inhibitor reduces sympathetically induced coronary vasoconstriction seems promising.
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PMID:Effects of converting enzyme inhibitors on coronary flow and myocardial ischemia. 138 90

The experiments were performed on 30 healthy mongrel dogs, intubation was taken in the left anterior descending coronary (LAD), the blood in carotid was transported to LAD through a peristalic pump, the blood flow was reduced to 3-5 ml/min, thus acute myocardial ischemia was produced. Basing on this condition, 0.1-0.16 ml bradykinin (2 ug/ml) was given into LAD coronary before recording to produce angina pectoris. The effects of electroacupuncture (EA) at "Neiguan" area on myocardial oxygen metabolism, pH of coronary sinus blood and myocardial contractile force were observed (EA intensity 5 volts, frequency 1-20 Hz). The results are as follows: 1. EA could reduce obviously A-V difference of blood oxygen capacity (Ca-vO2) and the rate of myocardium extracting oxygen (O2E), thus reduced obviously oxygen consumption of ischemic myocardium. 2. EA could reduce V-A difference of carbon dioxide partial pressure (Pv-aCO2), prevent the decrease of pH of coronary sinus blood (PHv), this indicated that EA could prevent accumulation of acidic metabolic products. 3. EA could increase myocardial developed tension (DT) of ischemic area, strengthen myocardial contractile force of ischemic area. Above results indicated that EA could reduce oxygen consumption of ischemic myocardium, prevent the decrease of pH of coronary sinus blood, thus myocardial cell acidosis was prevented, myocardial contractile force was strengthened. It might be the mechanism of acupuncture treating coronary heart disease.
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PMID:[Effect of electroacupuncture on myocardial oxygen metabolism and pH of coronary sinus blood during experimental angina pectoris]. 139 52

One objective of this study was to examine a mechanism for the inability of patients to distinguish esophageal pain from cardiac pain. Patients with esophageal disease and angina pectoris often perceive pain as originating from the same somatic fields. Another objective was to compare the effect of esophageal distension between animals with a non-inflamed or with an inflamed esophagus. For this study in anesthetized cats, we recorded extracellular action potentials from T2-T7 spinal neurons that responded to intraluminal distension of an untreated or a turpentine-inflamed distal esophagus. Threshold distension volumes were compared between these 2 groups of animals. Neurons also were examined for effects of intracardiac bradykinin injection and somatic stimuli. Results showed that spinal neurons responded to a smaller threshold distension volume when cells in animals with an inflamed distal esophagus were compared to cells in animals with a non-inflamed distal esophagus. Spinal neurons that received input from the distal esophagus also received convergent input from the heart and somatic fields. Our data supported the hypotheses that (1) referred pain from the distal esophagus resulted from activation of the same spinal neurons by visceral and somatic input, (2) pain originating from the distal esophagus and heart might be difficult to distinguish because of viscerosomatic and viscerovisceral convergence onto the same spinal neurons, and (3) an inflamed distal esophagus might be more sensitive to distension than a non-inflamed esophagus.
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PMID:Viscerosomatic convergence onto feline spinal neurons from esophagus, heart and somatic fields: effects of inflammation. 140 4

Plasma bradykinin and prostaglandin metabolism are related to the anginal pain modulating system in patients with ischemic heart disease. We carried out a placebo controlled single blind test of diltiazem (30 mg three times a day) in 15 patients with chronic stable angina. The effect of diltiazem was evaluated by exercise treadmill testing and 48-h ambulatory electrocardiographic monitoring. Plasma bradykinin, thromboxane B2, and 6-keto-prostaglandin F1 alpha levels were determined by radioimmunoassay prior to and during diltiazem therapy. Diltiazem significantly increased the exercise time and reduced episodes of angina. Diltiazem, however, did not appreciably improve either the frequency of silent myocardial ischemic episodes or the total duration of the silent myocardial ischemic episodes. Diltiazem also tended to decrease plasma bradykinin, thromboxane B2, and 6-keto-prostaglandin F1 alpha levels. When ischemic episodes on ambulatory electrocardiographic monitoring are categorized according to heart rate change at the onset of episode (type A, preceded by heart rate increase > or = 5 beats/min; type B, no preceding heart rate increase), diltiazem was only effective on type A ischemic episodes as well as on symptomatic ischemia. Further, bradykinin was significantly decreased by diltiazem only in patients with exercise-induced silent ischemia or no exercise-induced ischemia, while the thromboxane B2/6-keto-prostaglandin F1 alpha ratio was unaffected by the administration of diltiazem. Thus, silent and symptomatic ischemia may be associated with different bradykinin and prostaglandin responses.
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PMID:Effect of diltiazem on silent ischemic episodes, plasma bradykinin and prostaglandin metabolism. 145 74

In this study, the effect of bradykinin on coronary flow in the isolated rat heart was significantly potentiated when cysteine or the sulfhydryl-containing converting enzyme inhibitors captopril and zofenoprilat were administered simultaneously. In contrast, the effect of concomitant administration of enalaprilat only slightly increased the effect of bradykinin on coronary flow. In nitrate-tolerant hearts of rats pretreated with isosorbide dinitrate (15 mg daily), the increase in coronary flow by nitroglycerin and bradykinin was significantly less when compared to control hearts. The effect of captopril was not affected by pretreatment. The involvement of endothelium-derived relaxing factor (EDRF) in the effect of captopril was apparent from experiments with L-arginine, the precursor of EDRF, and L-NMMA, the "false" precursor of EDRF. L-Arginine increased the effect of captopril, whereas L-NMMA showed a competitive antagonism for the effect of captopril on coronary flow in the isolated rat heart. Clinically, the effect of captopril was studied in 10 patients with stable, exercise-induced angina pectoris that had been treated for 3 weeks with slow-release isosorbide dinitrate (20 mg four times daily). At day 7, a baseline exercise test was obtained. Subsequently, patients with chest pain and at least 1-mm ST-segment depression on the ECG during exercise were included. They received on day 14 and 21 either captopril (25 mg) or placebo 1 h before exercise testing in a randomized, double-blind, crossover design. Captopril significantly improved the combined score of maximal ST-segment depression, maximal workload, and time to angina when compared to placebo. No differences in the pressure-rate index at rest and during exercise were seen. These results indicate that the sulfhydryl group of certain angiotensin converting enzyme inhibitors can potentiate their effect on the endogenous nitrovasodilator EDRF. In the clinical situation, this may lead to an improved exercise performance in patients with stable angina pectoris during chronic nitrate treatment, independent of its systemic vascular effects.
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PMID:Converting enzyme inhibitors and the role of the sulfhydryl group in the potentiation of exo- and endogenous nitrovasodilators. 172 Aug 43

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

ACE inhibition may be useful in several manifestations of ischaemic heart disease, such as heart failure due to ischaemic cardiomyopathy. Recent evidence suggests that these effects may also be present in normotensive patients with ischaemic heart disease without heart failure. Theoretically, converting-enzyme inhibition, through coronary and systemic vasodilating effects and negative inotropic properties, should have a favourable effect on the myocardial oxygen supply/demand ratio and, hence, affect the incidence and severity of myocardial ischaemia. It is doubtful, however, whether these cardiac and extracardiac properties of ACE inhibitors really underlie its potential antiischaemic effects, at least in the average patient with ischaemic heart disease without concomitant heart failure and hypertension. Recent animal and human studies indicate that converting-enzyme inhibitors may modulate myocardial ischaemia by reducing ischaemia-induced circulating neurohumoral activation. It has been shown that, depending on the severity of ischaemia, the circulating renin-angiotensin system may become activated together with an increase in circulating catecholamine levels. ACE inhibition suppresses this neuroendocrine stimulation during ischaemia and modulates subsequent systemic and, presumably, also coronary vasoconstriction. In addition to these effects on circulating neurohormones, ACE inhibition could affect myocardial ischaemia through a number of local actions, e.g. modulation of tissue (cardiac) angiotensin II formation and bradykinin breakdown, stimulation of prostaglandin synthesis and, in the use of sulphydryl compounds, by affecting EDRF formation. Whether ACE inhibitors have clear antiischaemic effects in all clinical conditions is uncertain. Their efficacy to limit exercise-induced ischaemia has been questioned. In contrast, pacing-induced ischaemia in patients at rest is clearly prevented by ACE inhibition. This differential effect may be related to a more pronounced difference in circulating neurohormones during exercise per se. It also suggests that ACE inhibitors may be particularly useful as (additional) antiischaemic therapy in patients with angina at rest, e.g. unstable angina and the acute phase of myocardial infarction.
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PMID:Neurohumoral activation during acute myocardial ischaemia. Effects of ACE inhibition. 197 98

This study was designed to observe the effect of electroacupuncture applied at "Neiguan" point on myocardial Glucose (GLU) and Free fatty acid (FFA) metabolism of dogs with experimental myocardial angina, experimental myocardial angina model was set up in 20 healthy mongrel dogs with reducing the volume of blood flow of left anterior descending coronary (LAD) and intracoronary administration of bradykinin. The results showed that arterial-venous difference of glucose (GLUa-v) was increased significantly and arterial-venous difference of free fatty acid (FFAa-v) was decreased significantly after experimental myocardial angina. with prolongation of the period of myocardial ischemia and increase of the times of myocardial angina, in control group, GLUa-v was increased lightly and FFAa-v was markedly decreased (P less than 0.05), this showed that FFA uptake of ischemic myocardium was markedly decreased. Electroacupuncture at bilateral "Neiguan" point resulted significant decrease of GLUa-v and slight increase of FFAa-v. There were statistical significance between the two groups (P less than 0.05) in GLUa-v and FFA-v. Aterial blood free fatty acid had not significant change after experimental myocardial angina and electroacupuncture had not marked effect on it. The above results indicated that experimental myocardial angina result in metabolic disorders of myocardial glucose and free fatty acid. Electroacupuncture may reduce glucose uptake and increase free fatty acid uptake of ischemic myocardium. Thus improved metabolic disorder of ischemic myocardium.
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PMID:[Change of myocardial glucose and free fatty acid metabolism and effect of electroacupuncture on them during experimental myocardial angina]. 211 10


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