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)

1. There is increasing evidence that a substantial number of patients who suffer from angina have normal epicardial arteries (Syndrome X), and it has been suggested that these individuals have a generalized disorder of small vessels not confined to the intramyocardial vasculature. 2. Small arteries were therefore obtained from biopsies of skin and subcutaneous fat from nine normotensive patients with Syndrome X and nine matched control subjects. Vessels were dissected and mounted as ring preparations in a myograph for morphological and functional assessment. 3. Morphological measurements revealed a significant increase in media thickness/lumen diameter ratio in arteries from patients with Syndrome X. Contractile responses to U46619 were similar in arteries from patients and control subjects. Endothelium-dependent relaxation induced with acetylcholine and bradykinin was greater in arteries from patients although differences were not statistically significant. Endothelium-independent relaxation induced by forskolin and sodium nitroprusside was not different. 4. In conclusion, these data demonstrate that subcutaneous small arteries from patients with Syndrome X are characterized by increased media thickness/lumen diameter ratios, although contractile responses were normal. Additionally, endothelium-dependent relaxation was not impaired in arteries from these patients. Thus, no significant functional abnormalities were associated with the observed structural differences.
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PMID:Small artery structural alterations of patients with microvascular angina (syndrome X). 897 10

Several clinical characteristics of angina pectoris are reflected in the nature of the cardiac nervous system. The extent of silent ischemia, the slow onset of angina during the ischemic cascade, the diffuse character of the visceral component of the pain and the referred pain. Of putative myocardial pain messengers so far only adenosine fulfills Lewis criteria for a cardiac pain messenger. Dependent on the pattern of ischemic release, adenosine appears to stabilize or sensitize afferent cardiac nerves with silent or painful ischemia as a result. Through spatio-temporal summation sensitization may result in an alarm whereby the myocardium signals centrally its precarious state. The activity of adenosine-sensitized afferent nerves may become enhanced by additional stimuli such as potassium, protons, substance P and bradykinin. Primary and secondary afferents from the intrinsic and extrinsic intrathoracic cardiac nervous systems project towards the central nervous system via sympathetic and vagal elements. The main part of primary afferents have their cell bodies in extrinsic cardiac ganglia and only a minority in the dorsal root ganglia. No cardiotopical representation exists in the intrathoracic ganglia. The majority of neurons in intrinsic and extrinsic cardiac ganglia are interneurons integrating cardiac inotropic and vasomotor functions on a beat to beat basis. Multisynaptic transmission over secondary afferents may not only delay the anginal pain message; as somatic afferents also connect to the intrathoracic ganglia, these multisynaptic transmissions may also be a basis for referred pain or pain inhibition. Dorsal root afferents appear to convey only excitatory impulses. Probably due to interneurons, cardiac nodose ganglia activities can become either excitatory or inhibitory. Cardiocardiac reflexes occur from the axonal level up to the brain stem cerebral levels. The brain defense system including the basal ganglia and limbic system and the prefrontal but not the sensory cortex are activated during myocardial ischemia indicating its traumatic nature. The reflexogenic nature of angina pectoris is evident as in silent ischemia similar central nervous system activation occurs as in angina pectoris but with less intense prefrontal activation while in Syndrome X more intense activation occurs. Therapeutic interference of the reflex mechanism by sympathectomy, electrical stimulation or pharmacological interventions can counteract angina pectoris and relax the reflexogenic stress and vasomotor drive on the heart.
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PMID:Neurophysiological aspects of angina pectoris. 910 85

1. Activity of ischaemically sensitive cardiac visceral afferents during myocardial ischaemia induces both angina and cardiovascular reflexes. Increased production of bradykinin (BK) and cyclo-oxygenase products (i.e. prostaglandins (PGs)) occurs during myocardial ischaemia. However, the role of these agents in activation of ischaemically sensitive cardiac afferents has not been established. The present study tested the hypothesis that BK produced during ischaemia activates cardiac afferents through kinin B2 receptors. 2. Single-unit activity of cardiac afferents innervating the left ventricle was recorded from the left thoracic sympathetic chain (T1-T4) of anaesthetized cats. Ischaemically sensitive cardiac afferents were identified according to their response to 5 min of myocardial ischaemia. The mechanism of BK in activation of ischaemically sensitive cardiac afferents was determined by injection of BK (1 microgram kg-1 i.a.), des-Arg9-BK (1 microgram kg-1 i.a., a specific kinin B1 receptor agonist), kinin B2 receptor antagonists: HOE140 (30 micrograms kg-1 i.v.) and NPC-17731 (40 micrograms kg-1 i.v., cyclo-oxygenase inhibition with indomethacin (5 mg kg-1 i.v.) and NPC-17731 (40 micrograms kg-1 i.v.) after pretreatment with indomethacin (5 mg kg-1 i.v.). 3. We observed that BK increased the discharge rate of all eleven ischaemically sensitive cardiac afferents from 0.39 +/- 0.12 to 1.47 +/- 0.37 impulses s-1 (P < 0.05). Conversely, des-Arg9-BK did not significantly increase the activity of eleven ischaemically sensitive fibres (0.58 +/- 0.02 vs. 0.50 +/- 0.18 impulses s-1. HOE140 significantly attenuated the response of twelve afferents to ischaemia (0.61 +/- 0.22 to 1.85 +/- 0.5 vs. 0.53 +/- 0.16 to 1.09 +/- 0.4 impulses s-1). NPC-17731, another kinin B2 receptor antagonist, had similar inhibitory effects on six other ischaemically sensitive cardiac afferents (0.35 +/- 0.14 to 1.19 +/- 0.29 vs. 0.22 +/- 0.08 to 0.23 +/- 0.07 impulses s-1). Indomethacin significantly reduced the responses of seven afferents to ischaemia (0.35 +/- 0.13 to 1.89 +/- 0.48 vs. 0.40 +/- 0.10 to 0.76 +/- 0.24 impulses s-1). Indomethacin also significantly reduced the responses of six ischaemically sensitive cardiac afferents to BK (2.65 +/ 1.23 to 1.2 +/- 0.51 impulses s-1. In six cats pretreated with indomethacin, NPC-17731 attenuated the impulse activity of six ischaemically sensitive cardiac afferents (0.39 +/- 0.12 to 1.0 +/- 0.3 vs. 0.26 +/- 0.14 to 0.48 +/- 0.20 impulses s-1. 4. This study demonstrates that BK produced during ischaemia contributes to stimulation of ischaemically sensitive cardiac visceral afferents through activation of kinin B2 receptors. Furthermore, BK stimulates ischaemically sensitive cardiac visceral afferents through a mechanism that is, at least in part, independent of cyclo-oxygenase activation.
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PMID:Endogenous bradykinin activates ischaemically sensitive cardiac visceral afferents through kinin B2 receptors in cats. 970 10

Angina pectoris often results from ischemic episodes that excite chemosensitive and mechanoreceptive receptors in the heart. Ischemic episodes release a collage of chemicals, including adenosine and bradykinin, that excites the receptors of the sympathetic and vagal afferent pathways. Sympathetic afferent fibers from the heart enter the upper thoracic spinal cord and synapse on cells of origin of ascending pathways. This review focuses on the spinothalamic tract, but other pathways are excited as well. Excitation of spinothalamic tract cells in the upper thoracic and lower cervical segments, except C7 and C8 segments, contributes to the anginal pain experienced in the chest and arm. Cardiac vagal afferent fibers synapse in the nucleus tractus solitarius of the medulla and then descend to excite upper cervical spinothalamic tract cells. This innervation contributes to the anginal pain experienced in the neck and jaw. The spinothalamic tract projects to the medial and lateral thalamus and, based on positron emission tomography studies, activates several cortical areas, including the anterior cingulate gyrus (BA 24 and 25), the lateral basal frontal cortex, and the mesiofrontal cortex.
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PMID:Mechanisms of cardiac pain. 1009 85

Sensory neurons that innervate the heart sense ischemia and mediate angina. To use patch-clamp methods to study ion channels on these cells, we fluorescently labeled cardiac sensory neurons (CSNs) in rats so that they could later be identified in dissociated primary culture of either nodose or dorsal root ganglia (DRG). Currents evoked by a variety of different agonists imply the importance of lowered pH (</=7.0) in signaling ischemia. Acidic pH evoked extremely large depolarizing current in almost all cardiac afferent neurons from the DRG (CDRGNs). In contrast, only about half of the unlabeled DRG neurons responded to acid, and their current amplitudes were much less than that in CDRGNs. In all respects tested--kinetics, selectivity, and pharmacology--the acid-evoked current was similar to that of previously described native and cloned acid-sensing ion channels. Cardiac afferents from the nodose ganglia differed from CDRGNs in having smaller acid-evoked currents but clearly larger currents evoked by ATP. Serotonin, acetylcholine, bradykinin, and adenosine elicited currents in fewer CSNs than did ATP or lowered pH, and the currents were relatively small. Capsaicin, an activator of small nociceptive sensory neurons that innervate skin, evoked only small and rare currents in CDRGNs. The extremely large amplitude and prevalent expression of acid-evoked current in CSNs imply a critical role for acidity in sensation associated with myocardial ischemia.
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PMID:Acid-evoked currents in cardiac sensory neurons: A possible mediator of myocardial ischemic sensation. 1022 39

Acupuncture and electroacupuncture (EA) have been used in traditional Chinese medicine to treat a wide range of diseases and conditions, including angina pectoris and myocardial infarction. In a feline model of reflex-induced reversible myocardial ischemia, electrical stimulation of the median nerves to mimic EA (Neiguan acupoint) significantly improved ischemic dysfunction, secondary to an inhibitory effect of EA on reflex pressor effects evoked by bradykinin (BK). The central mechanism of EA's inhibitory effect in this model is unknown. Accordingly, in alpha-chloralose-anesthetized cats, BK (10 micrograms/ml) was applied to the gallbladder to elicit a cardiovascular reflex response that significantly (P < 0.05) increased arterial blood pressure and heart rate; normalized systolic wall thickening (%WTh) of the left ventricle, measured by ultrasonic single-crystal sonomicrometer, increased by 31 +/- 11% (P < 0.05). After ligation of a side branch of the left anterior descending coronary artery, the reflex pressor response to BK resulted in a significant decrease of %WTh (-32 +/- 6%) in the ischemic region. When bilateral EA of the Neiguan acupoints was performed, the pressor response to BK was inhibited and regional myocardial function was significantly improved (+19 +/- 20%). The inhibitory effects of EA on blood pressure and %WTh were reversed by intravenous injection of naloxone (0.4 mg/kg; n = 9) or microinjection of naloxone (10 nM in 0.1 microliter/site; n = 14) into the rostral ventrolateral medulla (rVLM). Thus %WTh with intravenous naloxone was reduced to -13 +/- 29% (P<0.05) during stimulation of the gallbladder. Our results indicate that the inhibitory effect of EA on the BK-induced pressor response and the consequent improvement of ischemic dysfunction is dependent on the activation of opioid receptors, specifically receptors located in the rVLM.
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PMID:Naloxone reverses inhibitory effect of electroacupuncture on sympathetic cardiovascular reflex responses. 1036 96

Chest pain can arise from cardiovascular or noncardiovascular causes. Among the latter are the skin, the chest wall, intrathoracic structures, or subdiaphragmatic organs. The problem to attribute the chest discomfort to either the heart or extracardiac organs arises because the heart, pleura, aorta, and esophagus are all supplied by sensory fibers from the same spinal segments. In contrast to the diseases mentioned above, angina pectoris in sensu strictu is defined as chest pain or discomfort of cardiac origin that arises because of temporary imbalance between myocardial oxygen supply and demand. The metabolic oxygen requirements of the myocardium are essentially dictated by myocardial contraction since only a fraction of the consumed oxygen is needed by the quiescent heart. Therefore, the factors that primarily influence myocardial oxygen consumption include heart rate, the force of cardiac contraction, and myocardial wall tension, as determined by pressure (afterload), volume (preload), and wall thickness. Extracoronary diseases, e.g. hypertensive heart disease, aortic stenosis or cardiomyopathies, can influence these factors and induce angina pectoris (Figure 1). On the other hand, different diseases influencing the oxygen supply, e.g. anemia, can cause angina pectoris, too. In addition, the modulation of the coronary tone by mediators and cytokines can cause angina, coronary spasm being one example. The neurophysiological substrate of angina pectoris are ganglia which are present within the heart, particularly in epicardial fat. The sympathetic nervous system is the main conveyer of afferent pain fibers from the heart and pericardium, but many fibers may travel by the vagus and the phrenic nerves. Therefore, multiple thoracic structures may cause similar pain syndromes in the distressed patient. The blood supply of intrinsic cardiac ganglia arises primarily from branches of the proximal coronary arteries. Adenosine, among a number of substances, can modulate the activity generated by cardiac afferent nerve endings and intrinsic cardiac neurones. During myocardial ischemia adenosine is released in large quantities into the interstitial space. Given as an intravenous bolus to healthy volunteers or to patients with ischemic heart disease and angina pectoris, adenosine provokes angina pectoris-like pain, which is similar to habitual angina pectoris with regard to quality and location. But other mediators (e.g. bradykinin, histamine, prostaglandins, potassium, lactate) can be involved in the development of angina pectoris, too. As most emphasis should be given to the most serious causes first, the cardiologist has to consider ischemic cardiac disease in the differential diagnosis of nearly every case of acute chest pain. The differential diagnosis contains several causes of nonischemic cardiac chest pain. Dissecting aortic aneurysm may cause severe anterior chest pain that can be mistaken for myocardial infarction. Patients frequently will note the sudden onset of the pain rather than the relatively slower onset of ischemic pain. Furthermore, they feel as a tear and describe it as the most severe pain they have ever had. Pericarditis can be characterized as a sharp precordial knife-like pain that is often increased by lying down, breathing, swallowing, or any other thoracic motion. Radiation of pericardial pain is often relieved by sitting up or leaning forward. It may involve the shoulders, upper back, and neck because of the irritation of the diaphragmatic pleura. Acute pulmonary embolism is associated with severe chest pain. It may mimic acute myocardial infarction. Pulmonary embolism should be suspected when dyspnea or tachypnea seems to be disproportionate to the severity of the chest pain. Diffuse esophageal spasm is the extracardiac condition that is confused most often with ischemic cardiac chest pain. This pain presents as a deep thoracic pain that may be present over most of the thorax. It may extend down the anterome
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PMID:[Angina pectoris in extracoronary diseases]. 1037 99

Cardiac sympathetic afferents are known to reflexly activate the cardiovascular system, leading to increases in blood pressure, heart rate, and myocardial contractile function. During myocardial ischemia, these sensory nerves also transmit the sensation of pain (angina pectoris) and cause tachyarrhythmias. The authors' laboratory has been interested in defining the mechanisms of activation of this neural system during ischemia and reperfusion. During these periods, reactive oxygen species, particularly hydroxyl radicals, are produced from the breakdown of purine metabolites and lead to stimulation of sympathetic (and vagal) ventricular chemosensitive nerve endings. For example, stimulation with hydrogen peroxide leads to a small reflex increase in blood pressure from the predominant sympathetic afferent activation that is reduced by simultaneous activation of cardiac vagal afferents (known to exert predominantly depressor reflexes). Central integration of these two opposing reflexes likely occurs at several regions of the brain stem, including the nucleus tractus solitarii, where neural occlusion occurs during simultaneous cardiac sympathetic and vagal-afferent stimulation. Activation of platelets also appears to play a role during myocardial ischemia, leading to local release of serotonin (5HT), which, through a 5HT3 mechanism, stimulates sympathetic afferents. Finally, regional changes in pH from lactic acid (but not hypercapnia), stimulate ventricular afferents and may activate kallikrein to increase bradykinin (BK), which, in turn, breaks down arachidonic acid to form prostaglandins. Prostaglandins sensitize cardiac sympathetic afferents to BK. Thus, stimulation of cardiac sympathetic afferents during ischemia and reperfusion and the resulting reflex events form a multifactorial process resulting from activation of a number of chemical pathways in the myocardium.
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PMID:Cardiac sympathetic afferent activation provoked by myocardial ischemia and reperfusion. Mechanisms and reflexes. 1145 9

The present study used a rat model in which algogenic chemicals were infused into the pericardial sac to evoke spasmlike contractions in paraspinal muscles. The following techniques were used to study the roles of sympathetic (SCA) and vagal cardiac afferents (VCA) in electromyographic (EMG) responses to pericardial algogenic chemicals: chemical stimulation, electrical stimulation, and nerve transection. Activation with bradykinin (n = 46) produced a significantly higher peak response than infusion of an algogenic mixture (n = 53) containing chemicals that also activate VCA. Electrical stimulation of SCA produced bilateral EMG activities (7 of 7). Electrical stimulation of VCA did not evoke EMG activity but inhibited the chemically evoked EMG response (12 of 12). The chemically evoked response was decreased after transection of the left sympathetic chain (n = 22) and was increased after bilateral vagotomy (n = 19). These results suggest an excitatory and inhibitory role for SCA and VCA, respectively. Therefore, in addition to spinothalamic convergence of somatic and visceral afferents, activation of SCA to generate spasmlike muscle contractions could account in part for anginal pain, and VCA activation could attenuate this effect.
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PMID:Afferent pathways for cardiac-somatic motor reflexes in rats. 1170 97

It is unclear whether coronary endothelial function is linked to the pathogenesis of coronary spastic angina (CSA), so the present study examined the coronary vasomotor responses to acetylcholine (ACh) and bradykinin (BK) in 23 patients with CSA, 26 patients with CSA+coronary artery disease (CAD), and 21 control patients. Acetylcholine induced vasospasm of the left coronary artery in all of the patients with CSA, but not in any of the control patients. The changes in dilatation of the left coronary artery in response to bradykinin at doses of 0.2, 0.6 and 2.0 microg/min in the CSA group were significantly greater than those in the other 2 groups. The ratio of epicardial coronary vasodilations induced by BK to those induced by nitroglycerin did not differ among any of the groups. Bradykinin caused a similar increase in coronary blood flow in the control group and CSA group, but had less of an effect in the CSA+CAD group. In conclusion, the vasorelaxing effect of BK was preserved not only in epicardial spasm coronary arteries induced by ACh, but also in resistance coronary arteries distal to the spasm arteries in patients with CSA. The coronary vasodilation response induced by BK may not deteriorate until coronary atherosclerosis advances in patients with CSA.
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PMID:Coronary vasomotor responses to bradykinin and acetylcholine in patients with coronary spastic angina. 1176 97


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