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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. In spontaneously beating preparations of sinus venosus of the frog Caudiverbera caudiverbera the electro-physiologic effects of verapamil on action potential parameters of both primary and transitional pacemaker cells were investigated. 2. Verapamil in concentrations ranging from 5 x 10(-8)M to 2 x 10(-6)M slowed the sinus rate and blocked impulse initiation. Action potential blockade was accompanied by oscillations of membrane potential and depolarization. 3. During blockade of primary pacemaker cells, pacemaker shift originated the activation of transitional or atrial contractile fibres. 4. Subthreshold concentrations of the drug to induce complete blockade (5 x 10(-8)M) allowed to observe a greater depression of bioelectric cell characteristics in primary than in transitional fibres. 5. Verapamil-induced blockade of transitional pacemaker action potentials was preceded by the appearance of a notch in their upstroke and the persistence of a fast depolarizing section that remained unblocked. This fast verapamil-resistant section of the upstroke was absent in preparations treated with tetrodotoxin (TTX). 6. The results confirmed most previously described actions of verapamil on mammalian sinoatrial preparations and provided a pharmacological dissection of the two slow and fast bio-electric components contributing to the upstroke of transitional pacemaker cells of the frog sinus venosus.
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PMID:Electrophysiological effects of verapamil on primary and transitional pacemaker cells of the frog heart. 341 5

Verapamil-induced cardiovascular depression has been examined in dial-urethane-anesthetized open chest dogs. Verapamil was administered slowly intravenously until the mean arterial pressure was decreased by approximately 45 mm Hg. The dose of verapamil required to reach the hemodynamic endpoint was 1,495 +/- (SE) 165 micrograms/kg. In a second group, interactions between beta-adrenergic blockade, propranolol 1 mg/kg (i.v.), and verapamil were examined. Although propranolol alone had only minor hemodynamic effects, the cardiac depressant dose of verapamil was reduced significantly to 450 +/- 105 micrograms/kg. After cardiovascular depression with verapamil or verapamil plus propranolol, glucagon was administered to assess its inotropic activity using cumulative doses of 5, 15, and 45 micrograms/kg over 20 min. Glucagon produced a dose-dependent recovery of heart rate, mean arterial pressure, and PR interval. Depressed contractility assessed by peak positive dP/dt and right ventricular isometric contractile force also recovered after glucagon. These results suggest a significant interaction between the potency of verapamil as a myocardial depressant and the state of the myocardium as affected by beta-blockade. Cardiac depression by verapamil or verapamil in combination with propranolol was reversible by glucagon.
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PMID:Cardiovascular depression by verapamil: reversal by glucagon and interactions with propranolol. 342

In this study prophylactic antiarrhythmic effects of verapamil on exercise-induced ventricular arrhythmias are evaluated. Investigations were carried out on a total of 22 patients. All patients showed frequent and/or complex ventricular arrhythmias during repeated exercise tests under control conditions. After two control exercise tests all patients were treated with verapamil 120 mg given every 8 hours orally over 4 days. On the 3rd and 4th day of treatment the exercise tests were repeated. Verapamil caused a significant reduction in the incidence and severity of exercise-induced ventricular arrhythmias in 13 out of 22 patients. In patients with exercise-induced ST-segment depression a prophylactic action could be demonstrated in 9 out of 10 cases. The antiarrhythmic effect was independent of changes in heart rate. A reduction in myocardial oxygen consumption and direct electrophysiological effects (suppression of the 'slow response' and/or an increase in the resting potential of the 'depressed fast response') can be considered, as well as a suppression of 'triggered activity' or a direct inhibition of adrenergic effects. Calcium antagonists (type verapamil) prove to be suitable drugs for the treatment of exercise-induced ventricular arrhythmias in patients with myocardial ischaemia.
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PMID:Prophylaxis of exercise-induced ventricular arrhythmias by verapamil. 344 31

The short- and long-term effects of two calcium channel blocking drugs, verapamil and nifedipine, on blood pressure, heart rate, plasma catecholamines, plasma renin activity, plasma volume and cardiac performance (echocardiography) were studied in essential hypertensive patients and in normal subjects. Verapamil, 160 mg orally, reduced blood pressure within 60 minutes in 22 hypertensive patients, but not in 12 normotensive subjects. Nifedipine, 10 mg sublingually, reduced blood pressure within 15 minutes in 19 hypertensive patients, but not in 7 normotensive subjects. Plasma noradrenaline was significantly increased both in normal subjects and in hypertensive patients only after nifedipine was administered. Verapamil (80 mg three times a day) first, and nifedipine (10 mg three times a day) thereafter, or vice versa, were given to 12 hospitalized hypertensive patients on a fixed sodium and potassium intake; the drugs produced similar blood pressure reductions, but heart rate and plasma catecholamines were increased only after nifedipine (p less than 0.05). Neither drug affected plasma volume, aldosterone or plasma renin activity. Long-term ambulatory treatment with verapamil (80 or 160 mg three times a day for 2 to 4 months) or nifedipine (10 mg three times a day for 2 months) produced changes in all variables that were similar to those observed in the hospital (controlled) study. Shortening fraction was significantly increased after nifedipine (p less than 0.05) but no change was observed after verapamil. In conclusion, blood pressure is effectively reduced by both verapamil and nifedipine; an appreciable adrenergic stimulation may be caused by nifedipine, but usually not by verapamil, and fluid retention, renin release or myocardial depression is not observed during verapamil or nifedipine treatment.
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PMID:Similarities and differences in the antihypertensive effect of two calcium antagonist drugs, verapamil and nifedipine. 351 29

Calcium antagonists constitute a group of organic compounds with diverse chemical structures. Although their main pharmacodynamic actions are vasodilatation and myocardial depression, they are not uniform in producing these effects. Based on comparison of the potencies in producing negative inotropic, chronotropic and dromotropic effects to the coronary vasodilator potency of individual calcium antagonists determined by use of isolated, blood-perfused papillary muscle, sinoatrial node and atrioventricular node preparations of dogs, calcium antagonists are classified into 2 major groups. The dihydropyridines, nicardipine, nifedipine, nimodipine, nisoldipine, nitrendipine, PN 200-110 (isradipine) and PY 108-068, are generally far more potent in producing coronary vasodilatation than in producing negative inotropic, chronotropic and dromotropic (first-degree atrioventricular block) effects, although there are minor differences among them. The non-dihydropyridine calcium antagonists, verapamil, diltiazem, KB-944, bepridil and MCI-176, are nearly equipotent in producing coronary vasodilatation and a negative dromotropic effect, although all of them are less potent in producing negative inotropy. The non-dihydropyridine calcium antagonists can be further divided into 2 subgroups. Verapamil, diltiazem and KB-944 are nearly equipotent in producing negative dromotropic and chronotropic effects. Bepridil and MCI-176 are less potent in producing negative chronotropy than in producing negative dromotropy.
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PMID:Differences in cardiovascular profile among calcium antagonists. 354 89

The efficacy and effect on cardiac function of verapamil 120 mg three times a day and atenolol 100 mg once a day, singly and in combination, were evaluated in 15 patients with angina pectoris. While they were on the combination treatment four patients withdrew from the study. Episodes of angina pectoris and glyceryl trinitrate consumption were significantly reduced only on the combination. On the combination only four patients developed evidence of ischaemia during exercise compared with seven on verapamil and ten on atenolol. ST segment depression at peak exercise, assessed by 16 point precordial mapping, was reduced by all active treatments from 7.1 on placebo to 2.7, 0.9, and 0.6 mm on atenolol, verapamil, and the combination respectively. Mean left ventricular ejection fraction fell significantly from 60% on placebo to 53% on the combination but was unchanged on verapamil and atenolol. Verapamil was an effective alternative to atenolol; the combination was the most effective treatment but was associated with a significant morbidity.
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PMID:A double blind placebo controlled comparison of verapamil, atenolol, and their combination in patients with chronic stable angina pectoris. 355 66

A comparison was made of effects of Mg, Ca, Sr, or verapamil on the mechanical and electrical activities in the uterine longitudinal muscles of spayed and estrogen-treated rats. The muscle strips taken from spayed rat exhibited spontaneous rhythmic activity in the Locke solution which did not contain Mg, whereas spontaneous activity was less frequent in the preparation taken from estrogen-treated rat. The resting potentials were -54 and -61 mV in the spayed and the estrogen-treated preparations, respectively. An initial spike potential followed by plateau potential with abortive spikes on the top was generated in both spayed and estrogen-treated preparations. In the spayed preparation, the frequency of rhythmic contractions was reduced, and the base-line tension was lowered when 0.6 mM Mg was added to the solution. The base-line tension was elevated progressively when the external Ca concentration was raised, and reached a maximal value up to 10 mM. The amplitude of phasic contraction was progressively increased by increasing Ca concentrations in the range from 1.25 to 5 mM, and was reduced by Ca higher than 10 mM. In the estrogen-treated preparation, the amplitude of phasic contraction was increased by increasing Ca concentrations in the range from 1.25 up to 17.5 mM. When the amplitude of phasic contraction was increased, the duration of plateau potential became protracted. Substitution of the external Ca with Sr caused an increase in the spike activity generated on the top of plateau potential. However, the amplitude of phasic contraction was diminished in both the spayed and the estrogen-treated preparations. Verapamil (2 microM) caused a stronger depression of electrical and mechanical activity in the spayed preparation. Results were discussed in relation to the genomic effects of estradiol on the membrane properties so as to change the interaction with divalent cations.
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PMID:Comparative effects of Mg, Ca, Sr, and verapamil on the uterine longitudinal muscle of spayed and estrogen-treated rats. 356 May 37

The effects of calcium entry blockers on stimulated cholesteryl [3H]-oleate deposition in cultured macrophages were characterized in order to elucidate mechanisms underlying possible antiatherosclerotic effects. Stimulation of intracellular cholesteryl [3H]-oleate deposition was initiated by incubation of macrophages with beta-very low density lipoproteins (beta-VLDL). Nifedipine (Class I) markedly reduced cholesteryl [3H]-oleate deposition at all concentrations tested. However, Bay K 8644, a dihydropyridine which is known to stimulate calcium entry, also reduced cholesteryl [3H]-oleate deposition with a similar potency to nifedipine. The effects of three Class II calcium entry blockers were evaluated: verapamil, methoxyverapamil, and diltiazem. Verapamil inhibited cholesteryl [3H]-oleate deposition in a concentration-dependent manner. Similarly, methoxyverapamil reduced cholesteryl [3H]-oleate deposition in a concentration-dependent manner although the reduction was not as great as that produced by verapamil. In contrast, diltiazem at any concentration tested did not inhibit cholesteryl [3H]-oleate deposition. Flunarizine (a Class III calcium entry blocker) produced a modest stimulation of cholesteryl [3H]-oleate deposition at the lowest concentration used (10(-7)M) but marked depression at the highest concentration (10(-5)M). The results indicate calcium entry blockers may exert protective effects on the development of atherosclerosis in animal models of diet-induced hyperlipidaemia by inhibiting intracellular cholesteryl ester deposition, but this effect may not be related to their calcium entry-blocking effects.
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PMID:Inhibition of cholesteryl ester deposition in macrophages by calcium entry blockers: an effect dissociable from calcium entry blockade. 359 69

Pretreatment of the ischemic myocardium with verapamil protects against mitochondrial respiratory depression observed during ischemic arrest as well as during reperfusion. Since ischemic mitochondrial function appears not to be altered further by reperfusion, the purpose of this study is to identify a biochemical event affecting mitochondria that is specifically associated with reperfusion injury. It has been proposed that increased cellular Ca2+ influx and oxygen toxicity may result from reintroduction of coronary flow. Increased cytosolic Ca2+ is transmitted to the mitochondria with subsequent activation of Ca2+-dependent events, including phospholipase A2. Net production of lysophospholipids (and loss of total diacylphospholipids from the mitochondria) will proceed when reacylation mechanisms are inhibited. Since acyl-CoA:lysophospholipid acyltransferase is a sulfhydryl-sensitive enzyme and since increased activity of glutathione peroxidase shifts the levels of the mitochondrial sulfhydryl buffer, glutathione, towards oxidation, levels of glutathione and its oxidation state were measured during reperfusion in the absence or presence of verapamil pretreatment. Ischemia lowers total glutathione and reduces the redox ratio (reduced glutathione: oxidized glutathione) by 85%. Reperfusion partially returns the redox ratio to control by causing oxidized glutathione to disappear from the matrix. Verapamil maintains both the concentration and the redox potential of glutathione at control levels. Concomitant with alterations in reduced glutathione:oxidized glutathione is a decrease in ischemic mitochondrial phospholipid content. During reperfusion, phosphatidylethanolamine and its major constituent fatty acids (C 18:0 and C 20:4) are specifically lost from the mitochondrial membrane. Accompanying the significant loss of arachidonic acid during reperfusion is the decreased content of 11-OH, 12-OH, and 15-OH arachidonate. These lipid peroxidation products are not increased in ischemia. It is proposed that oxidation of matrix glutathione to glutathione disulfide during ischemia results in formation of glutathione-protein mixed disulfides and inhibition of sulfhydryl-sensitive proteins, including acyl-CoA lysophosphatide acyltransferase. Thus, metabolic events occurring within the ischemic period set the stage for prolonged dysfunction during reperfusion.
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PMID:Protection by verapamil of mitochondrial glutathione equilibrium and phospholipid changes during reperfusion of ischemic canine myocardium. 362 93

Nifedipine, diltiazem and verapamil are three effective calcium-antagonists in the treatment of angina pectoris. We compared their effects on effort angina to evaluate whether one of them is more efficacious. The data were collected from 42 patients (37 males, 5 females; mean age 51 +/- 4) entering one of 3 different trials; the beginning of all trials comprised a two-week, single blind, placebo run-in phase. An exercise stress test was performed at the end of this period and it was considered as basal test for the statistical analysis. Then the 42 patients were divided in 3 groups of 14 and entered a double-blind, randomized phase of drug treatment. The 3 groups started 3 parallel trials: 1) placebo/nifedipine 60 mg/day; 2) placebo/verapamil 360 mg/day; 3) placebo/diltiazem 240 mg/day. The duration of each trial was of 6 weeks (3 weeks of treatment with placebo and 3 weeks with active substance). Exercise stress tests were performed at the end of each phase of the trials, and the resulting data were compared with the data of the test performed at the end of run-in period. Parameters evaluated were: heart rate, blood pressure and rate pressure product at basal conditions, at submaximal and peak exercise; moreover we considered workload, maximal ST segment depression, total exercise duration and frequency of exercise-induced angina. Verapamil reduced rate pressure product at basal condition; all three drugs reduced rate pressure product at submaximal exercise, but a significant statistical difference was found only for verapamil and diltiazem.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Comparative evaluation using an ergometric test of the efficacy of the 3 major calcium antagonists on exertion stable angina]. 365 91


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