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)

Retrospective analysis of information on 283 patients with myocardial infarction (186 males and 97 females) showed that 64.7% of persons who had suffered from the disease for the first time and 88.6% of those with recurrent myocardial infarction had a history of anginose pain. Exacerbation of angina pectoris had occurred in 56.0% of patients with no previous myocardial infarction and in 71,4% of those with recurrent infarction. A preinfarction state was encountered in primary and recurrent myocardial infarction with equal frequency (in 73.0 and 74.7% of cases, respectively). Nitroglycerin efficacy diminishes in the month preceding myocardial infarction. During exacerbation of angina pectoris, 39.8% of patients who had no previous myocardial infarction and 73.8% of those with a history of the disease applied for medical advice.
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PMID:[Retrospective evaluation of angina pectoris in patients with primary and recurrent myocardial infarct]. 720 44

A 54-year-old man, who was treated with propranolol for severe angina pectoris, developed severe symptomatic bradycardia during this treatment. Coronary angiography revealed severe coronary artery stenosis, but a bypass operation was judged to be technically impossible. When propranolol was withdrawn, the effort angina deteriorated and anginal pains even developed at rest. A favourable symptomatic effect was obtained with a combined regimen of propranolol and a permanent demand pacemaker. Nitroglycerin consumption was reduced from about 20 to less than 3 tablets a day. His condition remained stable during the observation period of 44 months. The symptomatic effect of a beta-blocking agent combined with a permanent pacemaker is considered to be due to the reduced inotropic and chronotropic effect of propranolol during exercise as well as the elimination of a bradycardia-induced angina at rest. Placebo effect to a certain extent cannot be excluded.
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PMID:Severe angina pectoris and BETA-blocker-induced bradycardia treated with an artificial pacemaker. 742 71

Nitroglycerin (NTG) has been used for more than a century for the relief of angina pectoris and is regarded as an extrinsic donor of nitric oxide (NO). Captopril, an angiotensin-converting enzyme inhibitor (ACEI), is reported to have beneficial effects on survival in acute myocardial infarction. In this study, a hybrid compound of NO and ACEI, S-nitrosocaptopril (S-NO-Cap), was synthesized, which was characterized by its molecular structure. Its coronary effects in chronically instrumented dogs were compared with those of NTG and captopril. S-NO-Cap (50 micrograms/kg i.v.) increased epicardial coronary diameter (CoD) by a maximum of 5.2% for more than 20 min. NTG (15 micrograms/kg i.v.) increased CoD by a maximum of 4.6% for 10 min, i.e., the effect was equipotent with that of S-NO-Cap (50 micrograms/kg i.v.). However, S-NO-Cap produced its maximal CoD increase more slowly than NTG did. Both S-NO-Cap and NTG transiently increased coronary blood flow. However, NTG had a more potent effect than S-NO-Cap (28.4 vs. 40.8 ml/min, respectively). Captopril, on the other hand, had almost no effect on either CoD or coronary blood flow. Thus, the vasodilatory action of S-NO-Cap more closely resembled that of NTG than that of captopril. Therefore, S-NO-Cap may dilate coronary arteries by virtue of its NO moiety rather than by its ACEI properties. These findings indicate that S-NO-Cap is a potential antianginal drug.
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PMID:The effects of S-nitrosocaptopril on canine coronary circulation. 761 25

Nitroglycerin (NTG) spray and sublingual tablets rapidly relieve an established attack of angina, and their infrequent use is not associated with the development of tolerance. Although, following a suitable nitrate-free interval, the first dose of oral, long-acting nitrates produces significant hemodynamic effects, increases angina free walking, and decreases exercise-induced ischemia, during continued long-term therapy tolerance limits their usefulness. Appropriate dosing regimens of controlled-release formulations of isosorbide dinitrate (ISDN) and controlled-release NTG during long-term therapy have not been established. Use of immediate-release formulation of 15-120 mg of ISDN in a qid regimen lead to a marked reduction in the size and duration of antianginal effects compared to the initial dose. Asymmetric tid therapy with 30 mg of ISDN (7 a.m., 1 p.m., and 6 p.m.) is also associated with the development of partial tolerance and appears to provide antianginal prophylaxis for only a period of 6 hours each day. Asymmetric bid therapy with ISDN at 7 a.m. and noon may give sustained effect but is supported by only a single, small study that did not examine effectiveness after the noon dose in long-term use. Isosorbide-5-mononitrate (IS-5-MN) has been the subject of more recent studies than other nitrates because of attempts to bring a number of products into the U.S. market. IS-5-MN in qid, tid, and standard bid (8 a.m. and 8 p.m.) dosing regimens produce tolerance. Asymmetric regimens of immediate-release IS-5-MN (10 and 20 mg) given bid (once in the morning and again 7 hours later) decrease the development of tolerance compared to symmetric regimens and produce an increased exercise duration after each dose of the day; the 20 mg bid dosing is more effective. Similarly, once-daily 120 and 240 mg controlled-release IS-5-MN does not produce tolerance and gives a sustained increase in daytime exercise duration. Both asymmetric bid immediate-release and once-daily controlled-release IS-5-MN preparations do not produce deterioration in exercise performance prior to the administration of the medication in the morning (i.e., no zero-hour effect). Further studies are needed to establish useful dosing regimens for ISDN, for controlled-release ISDN, and for controlled-release nitroglycerin. None of the dosing regimens of any oral, long-acting nitrate (including IS-5-MN) provide 24 hour antianginal and antiischemic effects.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Short and long-acting oral nitrates for stable angina pectoris. 784 96

Nitroglycerin (NTG) ointment is used for the prophylaxis against angina pectoris, but there are no data to support its effectiveness during long-term therapy. Continuous, once-daily application of isosorbide dinitrate cream produces tolerance with complete loss of efficacy within 1 week. Nitroglycerin patches are very popular and continuous once-daily application is still claimed by some investigators to provide 24 hour antiischemic and antianginal efficacy. This claim is based on data from postmarketing studies in a very large number of patients and placebo-controlled studies in smaller groups of patients from Italy, Yugoslavia, Greece, and Germany. In contrast, studies from the United States, Canada, England, and some centers in Germany have failed to show superiority of patches over placebo during continuous therapy. This controversy was addressed by the NTG cooperative study group, in which a total of 562 patients who were responders to sublingual nitroglycerin were studied. Patients received either placebo or NTG patches delivering low (15-30 mg/24 hr), moderate (45-60 mg/24 hr), or large (75 and 105 mg/24 hr) amounts of NTG. Four hours after the initial application, NTG patches increased exercise duration compared to placebo, but this beneficial effect had disappeared by 24 hours. Furthermore, after 8 weeks of continuous therapy, none of the NTG patches were superior to placebo, whether patients were or were not taking concomitant beta-blockers. Therefore, current opinion is that continuous therapy with NTG patches produces pharmacologic tolerance and is ineffective.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ointments and transdermal nitroglycerin patches for stable angina pectoris. 784 97

Glyceryl trinitrate, isosorbide dinitrate, and isosorbide-5-mononitrate are organic nitrate esters commonly used in the treatment of angina pectoris, myocardial infarction, and congestive heart failure. Organic nitrate esters have a direct relaxant effect on vascular smooth muscles, and the dilation of coronary vessels improves oxygen supply to the myocardium. The dilation of peripheral veins, and in higher doses peripheral arteries, reduces preload and afterload, and thereby lowers myocardial oxygen consumption. Inhibition of platelet aggregation is another effect that is probably of therapeutic value. Effects on the central nervous system and the myocardium have been shown but not scrutinized for therapeutic importance. Both the relaxing effect on vascular smooth muscle and the effect on platelets are considered to be due to a stimulation of soluble guanylate cyclase by nitric oxide derived from the organic nitrate ester molecule through metabolization catalyzed by enzymes such as glutathione S-transferase, cytochrome P-450, and possibly esterases. The cyclic GMP produced by the guanylate cyclase acts via cGMP-dependent protein kinase. Ultimately, through various processes, the protein kinase lowers intracellular calcium; an increased uptake to and a decreased release from intracellular stores seem to be particularly important.
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PMID:Mechanisms of action of nitrates. 787 67

Nitroglycerin provides an external source of nitric oxide which stimulates guanylate cyclase and produces vasodilatation and inhibition of platelet function. The antithrombotic effects of intravenous nitroglycerin were recently documented in various experimental models and in patients with unstable angina. This protocol was designed to evaluate whether these effects could also be detected with transdermal nitroglycerin in patients with stable angina. In a randomized, double-blind, controlled parallel trial, 22 patients received transdermal nitroglycerin, 0.6 mg/hour (11 patients), or placebo (11 patients). Platelet aggregation to adenosine diphosphate (ADP) and to thrombin was measured in whole blood. Thrombus formation was assessed on porcine aortic media exposed to the patient's venous blood for 3 minutes at shear rates of 2,546 and 754 s-1. Platelet aggregation to ADP decreased from 7.7 +/- 0.8 to 5.3 +/- 0.8 ohms (p < 0.05) with nitroglycerin, and to thrombin from 15.6 +/- 1.2 to 12 +/- 1.2 ohms (p < 0.05). Thrombus size at the high-shear rate decreased from 2.8 +/- 0.7 to 1.0 +/- 0.3 microns 2 (p < 0.05), and at the low-shear rate from 2.5 +/- 0.5 to 1.0 +/- 0.2 microns 2 (p < 0.05). Placebo had no significant effect on platelet aggregation and platelet thrombus deposition. These parameters were all reduced by > or = 20% in 8 patients taking nitroglycerin but only in 3 patients taking placebo (p < 0.05). Transdermal nitroglycerin significantly inhibits platelet aggregation and mural thrombus formation in patients with angina pectoris.
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PMID:Antithrombotic properties of transdermal nitroglycerin in stable angina pectoris. 819 30

Nitrates belong to the most potent drugs for treatment of angina pectoris. Patients with this disease always show arteriosclerotic changes in their coronary arteries. In arteriosclerotic vessels endothelium-dependent relaxation induced by the endogenous vasodilator nitric oxide (NO) is markedly reduced. This article introduces a theory, whereby NO production is not reduced in arteriosclerotic vessels (in the arteriosclerotic aorta of the rabbit it is even enhanced) but that the activity of superoxide dismutase, which normally metabolizes free oxygen-radicals (O2-) is reduced and that NO is metabolized by accumulating superoxides. It is interesting that only endogenous nitrate (NO) can be metabolized by this pathway, whereas in arteriosclerotic vessels exogenous nitro-vasodilatators remain fully effective. For the clinical use of nitrates it is of particular importance that these exhibit different potencies for epicardial coronary vessels and the myocardial microcirculation. Nitroglycerin causes extensive relaxation in isolated large coronary arteries but has only a limited effect on middle-sized vessels and almost none on arteries in the microcirculation. These differences in efficacy of nitroglycerin in the coronary micro- and macrocirculation is probably due to the inability of microvessels to transform nitroglycerin into active metabolites such as S-nitroso-L-cysteine. Comparing vascular and clinical effects of nitroglycerin (in particular dilatation of coronary vessels) and of adenosine (acting in particular on the coronary microcirculation) discloses the great importance of the aforementioned effects on epicardial coronary vessels for treatment of angina pectoris. In this context a vasodilatating effect on the coronary microcirculation might not only be disadvantageous but could even trigger angina pectoris itself.
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PMID:[Endogenous and therapeutic nitrates in healthy and arteriosclerotic blood vessels]. 824 89

Glyceryl trinitrate (GTN) mainly reduces systolic blood pressure (SBP) rather than diastolic blood pressure (DBP) in acute conditions. To examine the efficacy of GTN as an antihypertensive agent in patients with isolated systolic hypertension (ISH), the authors examined the effects of GTN on BP and arterial compliance (AC) in patients who underwent cardiac catheterization. Seventy patients (with old myocardial infarction, 36; angina pectoris, 25; chest pain syndrome, 9) who underwent cardiac catheterization because of chest pain were included in this study. They were aged between thirty-seven and seventy-four (mean sixty-one) years. According to the levels of BP at cardiac catheterization, the authors selected two subgroups: the normotensive group (NT group, n = 18) and the isolated systolic hypertensive group (ISH group, n = 20) from all subjects. The authors measured BP before and after (three minutes) sublingual administration of GTN (0.3 mg) at the cardiac catheterization. AC was assessed by means of diastolic pressure decay. The change of BP was estimated by the differences between values before and at three minutes after GTN. After administration of GTN, SBP was decreased significantly from 157 +/- 25 to 142 +/- 23 mmHg (P < 0.01), while DBP did not change (83 +/- 13 vs 84 +/- 15 mmHg). The change in SBP was positively correlated with the pretreatment SBP and negatively correlated with AC (r = 0.51, P < 0.001; r = 0.39, P < 0.001, respectively). AC was significantly lower in the ISH group than in the NT group (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of glyceryl trinitrate on blood pressure and arterial compliance. 828 72

The anti-ischemic heart effect of (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]- 5-nitro-3-hexenamide (FK409), a novel nitric oxide donor, was studied in dog and rat preparations in vivo and in vitro. In anesthetized dogs with partially occluded coronary artery that were subjected to atrial pacing at a constant blood pressure, FK409 (1-100 micrograms/kg, i.v.) suppressed the ST-segment elevation on epicardial electrocardiograms. Glyceryl trinitrate (GTN; 10, 32 micrograms/kg) or dipyridamole (1000 micrograms/kg) failed to suppress the ST-segment elevation, although continuous i.v. infusion of GTN (32, 100 micrograms/kg/min) was effective. FK409 also suppressed the ST-segment elevation induced by methacholine in anesthetized rats by both i.v. (10, 100 micrograms/kg) and intraduodenal (i.d., 100, 1000 micrograms/kg) injections, while GTN (100 micrograms/kg, i.v.; 1000 micrograms/kg, i.d.) was effective only by the i.v. route. FK409 (0.32 microgram/kg/min, i.v.) and GTN (10 micrograms/kg/min) increased the blood flows of the endomyocardium (ENDO) and the epicardium (EPI) and the flow ratio of ENDO/EPI in the ischemic zone in anesthetized dogs with occluded coronary artery. Furthermore, in isolated dog vascular preparations, FK409 (4.6 x 10(-10)-4.6 x 10(-7) M) had a greater vasorelaxing effect on the large coronary artery [2.0-2.5-mm outer diameter (od)] than on the small coronary artery (0.3-0.5-mm od) or the saphenous artery. The results suggest that FK409 protects against acute experimental myocardial ischemia through relaxation of the large conductive coronary artery, and may be a useful oral drug for the treatment of angina pectoris.
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PMID:Effect of FK409, a novel nitric oxide donor, on acute experimental myocardial ischemia. 841 78


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