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)

Developed for the treatment of migraine, sumatriptan is an agonist of 5-hydroxytryptamine-1-receptors. Though a pressure sensation is a common complaint, significant ECG changes have not been reported after subcutaneous administration of sumatriptan. A case history is given where angina pectoris after sumatriptan self-administration was experienced on two occasions by a 61-year old man with a history of minor myocardial infarction--without post-infarction angina--two years previously. The angina after sumatriptan was accompanied on both occasions by significant ST-segment depression on ECG-monitoring. An extracranial vasoconstrictor action of sumatriptan in patients with ischaemic heart disease is suggested.
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PMID:[Angina pectoris after sumatriptan (Imigran)]. 133 86

Platelet aggregation (PA), platelet thromboxane B2 (TXB2) generation and 14C 5-hydroxytryptamine (5HT) release were studied in 13 patients with unstable angina, and compared to 14 patients with stable angina and 16 healthy controls. A typical pattern, distinct in 4 aspects from stable angina patients or controls, was observed in the unstable angina patients. ADP or collagen induced shape change was 3-4 times greater, the extent of epinephrine induced PA was nil or very low, the extent of collagen induced 14C 5HT release was also reduced while collagen induced platelet TXB2 generation was increased in spite of a reduced extent of PA. The extent of ADP or collagen induced PA was also significantly reduced. These results indicate a platelet membrane abnormality occurring presumably during contact of the circulating platelets with a non-occlusive thrombus observed at sites of ruptured plaques in unstable angina patients. Since also the pattern (20-30% overlap with control values) was distinct from that of stable angina patients, it might indicate an active thrombotic process. Plasma beta-thromboglobulin (beta TG) and TXB2 levels and serum TXB2 generation were also studied in the cardiac patients and controls and in another 10 patients with advanced peripheral occlusive arterial disease (POAD). Plasma beta TG and TXB2 levels were slightly elevated in the unstable angina patients and markedly elevated in the POAD patients. Serum TXB2 generation was, however, elevated in the stable angina patients (p less than 0.002) and more so in the unstable angina patients (p less than 0.001) compared to controls or to POAD patients. This was presumably mediated through enhanced thrombin generation. These results suggest that the measured plasma beta TG variable in the unstable angina patients is not useful in the assessment of in vivo platelet activation. It is presumably reflecting the sum of local enhanced platelet activation (at sites of ruptured plaques) and of reduced function of the "defective" circulating platelets. The ability of the platelets of unstable angina patients to generate large amounts of TXB2 if occurring in vivo might induce an intense coronary vasospasm.
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PMID:Abnormal typical pattern of platelet function and thromboxane generation in unstable angina. 253 38

1. The effects of low oxygen tension on tone and on the responsiveness to contractile and relaxant agents were examined on circumflex coronary artery rings isolated from sheep. 2. When artery rings (2-2.5 mm o.d.) were set at their optimal resting tension, introduction of hypoxia (0% O2) caused a sustained contraction which was reversible on washing with oxygenated Krebs solution. In precontracted (40 mM KCl) arteries, hypoxia caused a similar response except that it was preceded by a transient relaxation. 3. The hypoxia-induced contraction was potentiated by the combination of phentolamine (1 microM) and propranolol (1 microM), markedly reduced by verapamil (10 microM) and either abolished or reduced by indomethacin (1 microM). Indomethacin itself caused a contraction. 4. Under hypoxic conditions, the contractile effects of U46619 (a stable thromboxane analogue) and 5-hydroxytryptamine (5-HT) and the vasodilator effects of noradrenaline, iloprost (a prostacyclin mimetic) and adenosine were markedly potentiated. In contrast, vasoconstriction to potassium or acetylcholine was depressed. 5. Changing the gases from 95% O2 to 12% O2 had no significant effect on the contractile effects of U46619. However, the maximum contractile effect of U46619 was significantly enhanced by changing the gases from 12% O2 to 0% O2. 6. Rings from a smaller branch (0.6-1.3 mm o.d.) of the circumflex coronary artery of the sheep, in the presence of hypoxia, exhibited qualitatively similar changes in the responsiveness to U46619, 5-HT and adenosine to those observed in the large artery. However, the effect of potassium was potentiated rather than depressed. 7. It is concluded that hypoxia-induced contraction may involve a modified release of cyclooxygenase products and be partly dependent upon the availability of extracellular calcium. 8. The change in the responsiveness of coronary arteries, under hypoxia, to both constrictor and dilator mediators may have clinical relevance to myocardial ischaemia and angina pectoris.
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PMID:Effects of hypoxia on the pharmacological responsiveness of isolated coronary artery rings from the sheep. 274 80

Studies were performed on isolated canine coronary artery segments to characterize the mechanism of the constrictor response of ergometrine (ergonovine), an agent used to induce coronary vasospasm in patients with variant angina. Changes in isometric tension were measured in coronary ring segments suspended in organ baths at 37 degrees C filled with a buffered salt solution. Single concentration-response curves were obtained in each tissue by cumulative addition of agonist. Maximum responses to 5-hydroxytryptamine (5-HT) were greater than for ergometrine or phenylephrine, but ergometrine had the lowest EC50. Alpha adrenoceptor block by prazosin (10 nM) or the irreversible antagonist benextramine tetrahydrochloride did not affect responses to 5-HT or ergometrine. Cyproheptadine and pizotifen (0.1-1 muM) depressed the ergometrine and 5-HT concentration-response curves with no change in the location of the EC50 values. Methysergide (0.01-1 muM) had concentration-dependent constrictor activity which was noncompetitively antagonized by cyproheptadine, but unaltered by benextramine tetrahydrochloride pretreatment. In addition, methysergide competitively antagonized the 5-HT and ergometrine concentration-response curves. Estimates of methysergide pKB values (-log dissociation constant) from computer analysis were 7.9 and 8.0 for the two agonists, respectively. It is concluded that methysergide is a partial 5-HT agonist, but cyproheptadine and pizotifen are noncompetitive 5-HT antagonists. Ergometrine is a potent 5-HT receptor agonist in canine coronary artery with negligable alpha adrenoceptor agonist activity.
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PMID:Ergometrine contracts isolated canine coronary arteries by a serotonergic mechanism: no role for alpha adrenoceptors. 611 72

The mechanism by which ergometrine provokes coronary vasospasm was investigated in vitro. Changes in tension were monitored isometrically on spiral strips of freshly obtained coronary (ventricular and circumflex branches) and basilar arteries from dogs. Cumulative concentration-response curves were established for noradrenaline, adrenaline, 5-hydroxytryptamine (5-HT), and ergometrine. The catecholamines either contracted or relaxed the coronary vascular smooth muscle by stimulating alpha- or beta-adrenoceptors, respectively, whereas both 5-HT and ergometrine consistently induced contraction of coronary arteries. In order to antagonize ergometrine-induced contraction on circumflex coronary arteries, appromimately 60-fold greater concentrations of phentolamine were required compared to those necessary for antagonism of noradrenaline. The concentration-response curve for noradrenaline was unchanged by ergometrine, indicating that the two compounds combine with different receptors. The use of the antagonists phentolamine, indoramine, pimozide, pizotifen, and methysergide provided evidence that ergometrine and 5-HT induce contraction of coronary arteries by stimulating the same type of 5-HT receptor, which, however, seems to be different from the 5-HT receptor present in basilar arteries. It is suggested that in Prinzmetal's variant form of angina, ergometrine can provoke coronary vasospasm by increasing the tone of the coronary vascular smooth muscle via stimulation of 5-HT receptors, thus reinforcing sympathetic coronary vascular tone.
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PMID:The mechanism of ergometrine-induced coronary arterial spasm: in vitro studies on canine arteries. 615 56

In this report we present the history of a patient with symptomatic carcinoid syndrome. During flushing he suffered from variant angina. The observation of coronary spasm due to excess 5-hydroxytryptamine (5-HT) is discussed with regard to the discharge of 5-HT from clotting platelets in the coronary arteries.
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PMID:Evidence for coronary spasm during flushing in the carcinoid syndrome. 646 96

Experiments were performed on isolated coronary arteries to determine whether or not lidoflazine, an agent reported to be beneficial in the treatment of angina pectoris, is effective in antagonizing coronary vasoconstriction. Segments of canine circumflex and right coronary arteries were suspended in organ chambers filled with aerated Krebs-Henseleit solution (37 degrees C) for continuous isometric tension recordings. Dose-dependent contractions were obtained with norepinephrine (in presence of propranolol) and 5-hydroxytryptamine; these contractile responses were antagonized by phentolamine and methysergide, respectively. Lidoflazine caused long-lasting, and dose-dependent inhibition of the responses to both norepinephrine and 5-hydroxytryptamine. High K+ solution (30 mM) caused sustained contraction of the coronary segments; these responses were depressed in a dose-dependent manner by lidoflazine. Lidoflazine slightly augmented relaxations caused by adenosine. Addition of Ca++ to the bath solution partially reversed the inhibitory effect of lidoflazine, which indicates that the compounds acts by inhibiting the influx of extracellular Ca++. Segments incubated in solution containing 20 mM K+ and subjected to anoxia exhibited transient contractions which were inhibited by lidoflazine. Ergonovine maleate caused contractures of the coronary arteries which also were antagonized in a dose-dependent manner by lidoflazine. These experiments demonstrate the ability of lidoflazine to counteract contractions of coronary vascular smooth muscles caused by factors which may be involved in the etiology of coronary vasospasm.
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PMID:Inhibitory effect of lidoflazine on contractions of isolated canine coronary arteries caused by norepinephrine, 5-hydroxytryptamine, high potassium, anoxia and ergonovine maleate. 735 66

The seronin or 5-hydroxytryptamine (5-HT) is a biogenic amine involved in diverse physiologic and physiopathological processes in the cardiovascular system. 5-HT may lower the arterial blood pressure by an action on central 5-HT1A receptors, or may increase it by stimulation of 5-HT2 receptors located in vascular smooth muscle. It has been postulated that hypofunction of 5-HT1A receptors, or the exaggerated stimulation of 5-HT2 receptor may be associated with arterial hypertension and that agonists of the first type (indorenate or 8-OH-DPAT) or antagonists of the second type (ketanserin or pelanserin) allow the control of arterial hypertension. On the other land, ketanserin and pelanserin attenuated the hemodynamic manifestations in an experimental model of thromboembolism, suggesting that 5-HT is involved in such phenomenon. Finally, 5-HT could be related with the presence of angor pectoris during hypertension or atherosclerosis, diseases that are associated with a lesional of the vascular endothelium, a condition that favors the 5-HT induced vasoconstriction in coronary arteries.
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PMID:[Serotoninergic receptors and cardiovascular diseases]. 765 75

Although serotonin (5-hydroxytryptamine; 5-HT) is used for provocation of coronary spasm, 5-HT receptor subtypes in spastic coronary arteries remain undetermined. We demonstrated the supersensitivity of isolated coronary artery to ergonovine, 5-HT, and sumatriptan, a 5-HT1D receptor agonist, in a patient with variant angina. Furthermore, we detected gene expression of 5-HT1Dbeta and 5-HT2A receptors in spastic coronary artery using RNase protection assay. These findings suggest that the leftward shift of the dose-response curve for 5-HT, which plays an important role in the pathogenesis of coronary spasm, is mediated by activation of 5-HT1Dbeta receptor.
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PMID:5-HT1Dbeta receptor mediates the supersensitivity of isolated coronary artery to serotonin in variant angina. 944 May 99

Ketanserin is a selective 5-hydroxytryptamine (5-HT2) antagonist with vasodilator properties in the systemic and pulmonary circulation. Ketanserin also can inhibit serotonin-induced coronary artery vasoconstriction during percutaneous transluminal coronary angioplasty (PTCA). The in vivo effect of ketanserin on the coronary arteries of patients with stable angina has not previously been reported. The effects of intravenous ketanserin on cardiac haemodynamics and coronary artery diameter were measured in 10 patients with stable angina undergoing diagnostic cardiac catheterisation. Ketanserin (10 mg, i.v.) was associated with significant reductions in systemic and pulmonary arterial pressure (p < 0.05) and total systemic (SVR) and pulmonary (PVR) vascular resistance (p < 0.05). No significant change in mean coronary artery diameter or coronary artery stenotic index was evident after ketanserin. Vasodepressor responses in the systemic and pulmonary arterial circulation were observed after ketanserin injection. We assume these responses to be a direct effect of ketanserin, although non-drug-induced changes over time cannot be excluded. No significant effect on coronary artery diameter was observed, presumably because circulating serotonin levels are low in patients with stable anginal symptoms.
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PMID:Effect of ketanserin on central haemodynamics and coronary circulation. 986 5


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