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

Verapamil is used clinically as a Ca(2+) channel inhibitor for the treatment of various disorders such as angina, hypertension and cardiac arrhythmia. Here we study the effect of verapamil on the bacterium Escherichia coli. The drug was shown to inhibit cell division at growth sub inhibitory concentrations, independently of the SOS response. We show verapamil is a membrane active drug, with similar effects to dibucaine, a local anesthetic. Thus, both verapamil and dibucaine abolish the proton motive force and decrease the intracellular ATP concentration. This is accompanied by induction of degP expression, as a result of the activation of the RpoE (SigmaE) extra-cytoplasmic stress response, and activation of the psp operon. Such effects of verapamil, as a membrane active compound, could explain its general toxicity in eukaryotic cells.
 ...
PMID:Verapamil, a Ca2+ channel inhibitor acts as a local anesthetic and induces the sigma E dependent extra-cytoplasmic stress response in E. coli. 1683 75

Ubiquinone (coenzyme Q10) is an obligatory component of the respiratory chain in the inner mitochondrial membrane coupled to ATP synthesis and acts as an antioxidant. Its additional localization in the different subcellular fractions is probably associated with its multiple functions in the cell. Coenzyme Q10 deficiency has been observed in patients with congestive heart failure, angina pectoris, coronary artery disease, cardiomyopathy, hypertension, mitral valve prolapse. The clinical benefits of Q10 supplementation in prevention and treatment of cardiovascular diseases have been observed in many trials. Ubiquinone is the introduction of the metabolic drugs and may be recommended to patients with cardiovascular pathologies as an adjunct to conventional treatment.
 ...
PMID:[Physiological aspects of ubiquinone supplementation in cardiovascular pathology]. 1717 44

The extracts from the roots of Salvia miltiorrhiza Bunge (Danshen) are widely and traditionally used in the treatment of angina pectoris, acute myocardial infarct, hyperlipidemia and stroke in China and other Asian countries. In this study, we have investigated the role of P-glycoprotein (P-gp) in the intestinal absorption of tanshinone IIA (TSA), a major active constituent of Danshen, using several in vitro and in vivo models. The oral bioavailability of TSA was about 2.9-3.4% in rats, with non-linear pharmacokinetics when its dosage increased. In a single pass rat intestinal perfusion model, the permeability coefficients (P(app)) based on TSA disappearance from the luminal perfusates (P(lumen)) were 6.2- to 7.2-fold higher (P < 0.01) than those based on drug appearance in mesenteric venous blood (P(blood)). The P(blood), but not P(lumen), was significantly increased when co-perfused with verapamil, or quinidine (both P-gp inhibitors). The uptake and efflux of TSA in confluent Caco-2 cells were significantly altered in the presence of verapamil, quinidine, MK-571, or probenecid. The transport of TSA across Caco-2 monolayers was pH-, temperature- and ATP-dependent. Furthermore, the transport from the apical (AP) to basolateral (BL) side of the Caco-2 monolayers was 3.3- to 8.5-fold lower than that from the BL to AP side, but such a polarized transport was attenuated by co-incubated verapamil or quinidine. A polarized transport was also observed in the control MDCKII cells and more apparent in MDR1-MDCKII monolayers, with the P(app) values of TSA in the BL-AP direction being 7- to 9-fold higher in MDR1-MDCKII monolayers than those in the control MDCKII cells. Moreover, TSA significantly inhibited P-gp-mediated transport of digoxin in P-gp-overexpressing membrane vesicles with an IC(50) of 2.6 microM, but stimulated vanadate-sensitive P-gp ATPase activity with estimated K(m) and V(max) values of 10.70 +/- 0.69 microM and 67.65 +/- 1.31 nmol/min/mg protein, respectively. TSA was extensively metabolized to tanshinone IIB (TSB), and two other oxidative metabolites in rat liver microsomes, but the formation rate of TSB in rat intestinal microsomes was only about 1/10 of that in liver microsomes. These findings indicate that TSA is a substrate and reversing agent for P-gp; and P-gp-mediated efflux of TSA into the gut lumen and the first-pass metabolism contribute to the low oral bioavailability. Further studies are needed to explore the role of other drug transporters and first-pass metabolism in the low bioavailability of TSA.
 ...
PMID:Role of P-glycoprotein in the intestinal absorption of tanshinone IIA, a major active ingredient in the root of Salvia miltiorrhiza Bunge. 1750 22

Myocardial ischemia is associated with reduced ATP fluxes and decreased energy supply resulting in disturbances of intracellular ion homeostasis in cardiac myocytes. In the recent years, increased persistent (late) sodium current was suggested to contribute to disturbed ion homeostasis by elevating intracellular sodium concentration with subsequent elevation of intracellular calcium. The new anti-ischemia drug ranolazine, a specific inhibitor of late sodium current, reduces sodium overload and hence ameliorates disturbed ion homeostasis. This is associated with symptomatic improvement of angina in patients. Moreover, ranolazine was shown to exhibit anti-arrhythmic effects. In the present article, we review the relevant pathophysiological concepts for the role of late sodium inhibition and summarize the most recent data from basic as well as clinical studies.
 ...
PMID:Mechanism of action of the new anti-ischemia drug ranolazine. 1804 26

Adenosine 5'-triphosphate (ATP) is implicated in peripheral pain signaling through activation of P2X receptors. P2X(3) receptors have a high level of expression in, and selective location on sensory afferents. P2X receptors, particularly the P2X(3) subtype, are identified as targets for novel analgesics. The stellate ganglion (SG) is peripheral sympathetic ganglia involved in heart function. Surgical interventions of sympathetic afferent pathways abolish or relieve angina pectoris, so it is showed that cardiac pain is mediated by the activation of afferents in sympathetic nerves. The cervicothoracic sympathetic ganglia, including the stellate ganglion, are implicated in sensations associated with myocardial ischemia or cardiac pain. In the present study we have examined P2X(3) involvement in cardiac nociceptive transmission. P2X receptor agonists activated currents (I(ATP)) in SG neurons. The I(ATP) amplitude and P2X(3) mRNA expression in myocardial ischemic injury group were much larger than those obtained in control group. Prostaglandin E(2) (PGE(2)) and substance P (SP) increased ATP-activated currents. P2X(3) receptor antagonist A-317491 reduced P2X agonist activated currents and P2X(3) mRNA expression. The results revealed that the myocardial ischemia induced the upregulation of P2X(3) receptor in function and morphous and P2X(3) receptor antagonist A-317491 inhibited P2X agonist activated currents and P2X(3) mRNA expression. The facts indicated that P2X(3) receptor in SG neurons was involved in cardiac nociceptive transmission.
 ...
PMID:Myocardial ischemic nociceptive signaling mediated by P2X3 receptor in rat stellate ganglion neurons. 1815 99

The objectives of this study were to determine the prevalence of metabolic syndrome (MS) and its component risk factors among Filipinos using three sets of criteria and to evaluate the association between MS and atherosclerotic cardiovascular disease and diabetes mellitus. The study utilised a multi-staged cluster sampling design. The prevalence of MS was found to be 11.9% by National Cholesterol Education Program/Adult Treatment Panel (NCEP/ATP III) criteria, 14.5% by International Diabetes Federation (IDF) criteria and 18.6% by NCEP/ATP III criteria modified by the American Heart Association/National Heart, Lung and Blood Institute (NCEP/ATP III-AHA/NHLBI) criteria. Low levels of high-density lipoprotein cholesterol (HDL-C) occurred in 60.2% of men and 80.9% of women. Abdominal obesity was noted in 17.7% of men and 35.1% of women. Blood pressure (BP) > or = 130/85 mmHg was seen in 33.3%, hypertriglyceridaemia in 20.6% and fasting blood sugar > or = 100 mg/dL (5.55 mmol/L) in 7.1%. Age-adjusted odds ratios showed that MS, by all three definitions, predisposed an individual to diabetes mellitus (DM) and stroke while MS by the IDF definition predisposed an individual to myocardial infarction (MI). Individuals with MS did not have a significant predisposition to angina and peripheral artery disease (PAD). Thus, the metabolic syndrome is common in Filipinos, with low HDL-C as the most prevalent component. The metabolic syndrome predisposes to diabetes mellitus and stroke, with a tendency to MI using the IDF criteria.
 ...
PMID:Metabolic syndrome in the Philippine general population: prevalence and risk for atherosclerotic cardiovascular disease and diabetes mellitus. 1839 11

Potassium (K(+)) channel openers are a diverse group of compounds which are used for the treatment of diseases like angina pectoris, hypertension, congestive heart failure, anti-hypoglycemic (insulinoma), bronchial asthma, etc. R/S-3,4-dihydro-2,2-dimethyl-6-halo-4-(substituted phenylaminocarbonylamino)-2H-1-benzopyrans are a new series of ATP-sensitive potassium (K(ATP-pbeta)) channel openers selective towards pancreatic beta-cells. QSAR modelling was done on these series of compounds to find a more active and selective K(ATP-pbeta) channel opener selective towards beta-cells of pancreatic tissues. Wang-Ford charges, partition coefficient, molar refractivity, principle moment of inertia at X, Y and Z axes are used as predictor variables and logarithm of percentage of residual insulin secretion is treated as response variable for the modelling. Multiple linear regressions with factor analysis were performed to develop QSAR models. Four equations were obtained using different combinations of the predictor variables based on factor loadings. Regression coefficients of all descriptors used are significant at more than 95% level. Results showed that Wang-Ford charges on atom numbers 11, 17, 18, 19 and 21 are important for the inhibition of residual insulin secretion. The presence of electron withdrawing group at m- and p-position of phenyl ring B is required for the inhibition. The energy minimized geometry of the most active compound supported our modelling.
 ...
PMID:QSAR modelling of pancreatic beta-cell KATP channel openers R/S-3,4-dihydro-2,2-dimethyl-6-halo-4-(substituted phenylaminocarbonylamino)-2H-1-benzopyrans using MLR-FA techniques. 1842 Mar 11

Alterations of cardiac metabolism can be present in several cardiac syndromes. Heart failure may itself promote metabolic changes such as insulin resistance, in part through neurohumoral activation, and determining an increased utilization of non-carbohydrate substrates for energy production. In fact, fasting blood ketone bodies as well as fat oxidation have been shown to be increased in patients with heart failure. The result is depletion of myocardial ATP, phosphocreatine and creatine kinase with decreased efficiency of mechanical work. A direct approach to manipulate cardiac energy metabolism consists in modifying substrate utilization by the failing heart. To date, the most effective metabolic treatments include several pharmacological agents, such as trimetazidine and perhexiline, that directly inhibit fatty acid oxidation. These agents have been originally adopted to increase the ischemic threshold in patients with effort angina. However, the results of current research is supporting the concept that shifting the energy substrate preference away from fatty acid metabolism and toward glucose metabolism could be an effective adjunctive treatment in patients with heart failure, in terms of left ventricular function and glucose metabolism improvement. In fact, these agents have also been shown to improve overall glucose metabolism in diabetic patients with left ventricular dysfunction. In this paper, the recent literature on the beneficial therapeutic effects of modulation of cardiac metabolic substrates utilization in patients with heart failure is reviewed and discussed.
 ...
PMID:Metabolic therapy of heart failure. 1899 75

Dipyridamole, an inhibitor of adenosine uptake as well as a cGMP phosphodiesterase inhibitor, is commonly used in prophylactic therapy for patients with angina pectoris. However, the effects of dipyridamole on systemic blood vessels, especially on the peripheral vascular system, are not well understood. Therefore, the effect of dipyridamole on ATP-induced arteriole contraction was examined with special reference to intracellular Ca(2+) concentration ([Ca(2+)](i)) using real-time confocal microscopy. In cases of 0.1-10microM range, dipyridamole induced only slight [Ca(2+)](i) decreases in smooth muscle cells of both testicular and cerebral arterioles. However, 100microM dipyridamole induced substantial [Ca(2+)](i) decreases in the cells. In the presence of 10microM dipyridamole, changes in ATP-induced [Ca(2+)](i) were found to be inhibited in smooth muscle cells of testicular arterioles but not in those of cerebral arterioles. In addition, alpha, beta-methylene ATP-induced [Ca(2+)](i) increases in testicular arteriole smooth muscle cells were also partially inhibited in the presence of dipyridamole. When testicular arterioles were perfused with dipyridamole, no increases in nitric oxide levels were detected. High levels of K(+) induced a [Ca(2+)](i) increase in testicular arterioles that was also partially inhibited by dipyridamole. In the presence of substances that affect protein kinase A or G, ATP-induced [Ca(2+)](i) was not completely inhibited. These findings suggest that dipyridamole may act not only as an inhibitor of adenosine uptake and as a cGMP phosphodiesterase inhibitor, but also as a calcium channel blocker in arteriole smooth muscle cells.
 ...
PMID:Dipyridamole inhibits intracellular calcium transients in isolated rat arteriole smooth muscle cells. 1935 6

Objective of our study was to estimate the metabolic syndrome (MSy)' components in type 2 diabetic subjects (T2D) with symptomatic coronary artery disease (CAD): arterial hypertension, waist circumference, triglyceridemia and plasma level of HDL, in order to define their clinical role in angina severity status. Second objective was to compare Adult Treatment Panel (ATP III) and International Diabetes Federation (IDF) criteria in testing of association MSy with current coronary status of population. Three hundred and twenty seven pts with T2D and manifested CAD were randomly included in a survey. Angina severity was assessed with the Canadian Cardiovascular Society (CCS). Data relieved MSyand its components, defined by ATP III, with predictive role for advanced angina stages. Presence of MSy is predictive for CCS3 angina severity (OR 9,93, 95% CI 0,78-126,28). Increased waist is a predictor for CCS3 (OR 1,22, 95% CI 0,27-5,46) and CCS4 symptoms onset (OR 1,55, 95% CI 0,36-6,73). CCS4 severity symptom is independently associated with arterial hypertension (OR 3,72, 95% CI 1,03-13,40) and hypertriglyceridemia (OR 1,72, 95% CI 0,42- 7,00). MSy components: increased waist, arterial hypertension and hypertriglyceridemia have been found predictive for angina CCS4 stage in T2D subjects, when IDF criteria were used. These findings raise the question of importance of metabolic syndrome and its individual constellations in T2D subjects with CAD. Results indicate that both criteria ATP III and IDF are reliable to define MSy in predictive model for coronary clinical status in T2D population.
 ...
PMID:Clinical role of estimation metabolic syndrome's components in type 2 diabetic population with symptomatic coronary artery disease--a comparison of two criteria. 2064 5


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>