Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Microscopic, myofilament motion caused by spontaneous oscillatory Ca2+ release from the sarcoplasmic reticulum (SR) of unstimulated rat papillary muscles produces scattered light intensity fluctuations (SLIF) in a laser beam scattered by the tissue. SLIF frequency increases with Ca2+ loading of resting muscle. We used novel time-gated SLIF measurements to determine how electrical stimulation (which per se both induces SR Ca2+ release and modulates total cellular Ca2+ loading) affects SLIF. Stimulation of thin rat, right ventricular muscles at 1 Hz in bathing [Ca2+] (Ca0) of 1.5 mM at 29 degrees C abolished SLIF for 5-7 seconds; SLIF then reappeared and monotonically increased for 10-15 seconds to reach the steady resting level. Resting force transients paralleled those of SLIF. The magnitude of depression and time course of recovery of both resting force and SLIF at this Ca0 vary inversely with the rate of prior stimulation and the number of stimuli given. An increase in Ca0 or disablement of the Na-K pump increased both resting SLIF and force; transient stimulation under these conditions (i.e., in a 2.5-5.5-second "diastolic window" after cessation of stimulation) augmented SLIF and force above the resting level. Isoproterenol caused a modest reduction of resting SLIF, but it transiently increased SLIF after stimulation up to 10-fold above the resting level. Nifedipine did not affect resting SLIF but transiently depressed SLIF after stimulation. Ryanodine abolished SLIF both after stimulation and at rest.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bimodal effect of stimulation on light fluctuation transients monitoring spontaneous sarcoplasmic reticulum calcium release in rat cardiac muscle. 318 Mar 58

The authors performed a long-term, double-blind, crossover, randomized study on the effects of two drugs (atenolol, 100 mg/day, or nifedipine, 10 mg t.i.d.) when administered alone or in combination on the exercise tolerance in 10 patients with stable angina on effort (mean age 52 +/- 4 years, 8 males and 2 females) and documented significant (greater than or equal to 70%) obstructive coronary lesions at angiography. None of the drug treatments improved exercise duration or maximal sustained work load. Atenolol decreased significantly ST segment depression to -1 +/- 0.8 from -1.91 +/- 0.7, baseline and -2.05 +/- 0.5, placebo. Nifedipine was not better than placebo. The atenolol plus nifedipine treatment was better than placebo (p less than 0.001) or nifedipine alone (p less than 0.05) but was not more significantly efficacious than atenolol alone. Long-term management of exertional angina can be usefully performed using atenolol. The use of nifedipine at the present dose of 10 mg, although well tolerated, did not improve the ST signs of ischemia.
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PMID:Atenolol and/or nifedipine in effort angina: which is the treatment of choice for exercise coronary protection? 319 3

1. Nifedipine and DHM9 (carboxymethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate) were studied for their effects on arrhythmias resulting from regional myocardial ischaemia in conscious rats, and for their effects on left ventricular developed pressure in vitro. 2. Nifedipine possessed antiarrhythmic activity at a high dose of 10 mg kg-1 i.v., but not at 0.5 or 2 mg kg-1. Ventricular fibrillation (VF), tachycardia (VT), and ventricular premature beats (VPB) were all attenuated to a similar degree; nifedipine did not have a selectivity of action for high frequency arrhythmias. 3. Before coronary occlusion, the three doses of nifedipine reduced arterial blood pressure by a similar magnitude, indicating a similar (maximal) degree of systemic vasodilatation. The reductions in blood pressure were accompanied by reflex tachycardia. Heart rate and blood pressure did not correlate with the incidence or severity of arrhythmias. 4. DHM9 had no influence on arrhythmias, haemodynamic variables or the ECG, even at 20 mg kg-1 i.v. 5. Nifedipine concentration-dependently reduced contractility in perfused paced (5 Hz) rat ventricles in vitro. Raising the concentration of K+ in the perfusion fluid from 3 to 10 mequiv.l-1 increased the potency (-log10 EC50) of nifedipine up to four fold, and caused a significant depression in excitability. 6. DHM9 at up to 3 x 10(-5) M had no significant influence on ventricular contractility in vitro. 7. The results provided indirect evidence in support of the hypothesis that calcium antagonists inhibit ischaemia-induced arrhythmias by virtue of inhibition of the slow inward current (Isi) in the ischaemic ventricular myocardium.
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PMID:The mechanism of action of calcium antagonists on arrhythmias in early myocardial ischaemia: studies with nifedipine and DHM9. 320 85

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

The ability of prostacyclin to relax human brain arteries contracted by different vasotropic agents has been investigated. Prostacyclin relaxation effect was less marked in atherosclerotically damaged vessels. Nifedipine was demonstrated to potentiate relaxation effect of prostacyclin at the level of sarcolemmal calcium transport, while cavinton and dipyridamole had an analogous influence, redistributing calcium in the intracellular stores. The potentiating effect of these drugs was also less pronounced in affected vessels, which might be connected to the depression of transport ATPase activity in the vascular smooth muscle cells.
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PMID:[Effect of prostacyclin on the cerebral vessels and its pharmacological modification]. 354 75

In patients with congestive heart failure (CHF) due to dilated cardiomyopathy, nifedipine, diltiazem and several of the newer calcium antagonists including nicardipine, nitrendipine, felodipine and PN 200-110 (isradipine) improve left ventricular function. Because of its relatively more pronounced negative inotropic and chronotropic actions, verapamil is generally not tolerated by patients with left ventricular failure. In addition, even relatively vascular-selective agents such as nifedipine can occasionally cause significant left ventricular depression, particularly if combined with beta-adrenergic blocking agents. Comparative studies using nitroprusside to cause an equivalent decrease in arterial pressure indicate that nifedipine acts predominantly on the arterial vasculature, and that a small but significant decrease in contractility occurs, apparently due to a direct myocardial action. Although diltiazem causes a depression in myocardial contractility in dogs with volume overload heart failure, limited data show no significant negative inotropic action in patients with heart failure. The negative inotropic effects, if any, of newer and possibly more vascular-selective agents are not yet known. Calcium antagonists appear to act predominantly on the limb and coronary vasculature, with relatively less effect on renal and hepatic vessels. In patients with CHF, nifedipine causes an increase in coronary blood flow and a decrease in the aorto-coronary sinus oxygen difference indicating an improvement in myocardial energetics. Although nifedipine causes an increase in cardiac index and decreases in systemic vascular resistance and pulmonary capillary wedge pressure during exercise, the limited data available fail to show a short- or long-term increase in exercise capacity. Nifedipine causes an increase in plasma renin activity, possibly due to a direct action on the kidney.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Usefulness of calcium antagonists for congestive heart failure. 354 90

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

The effects of nine calcium ion antagonists on exercise tolerance, heart rate and ST-segment changes were compared with those of propranolol in two hundred and eighty patients with established chronic stable angina pectoris. These patients participated in clinical trials for anti-anginal efficacy against placebo, using identical methods and similar protocols, but the comparison reported here was retrospective. The trials were all fixed dose, and the dose was determined by previous upward titration to arrive at an average maximal tolerance level. All the drugs except prenylamine increased the exercise tolerance significantly when compared with placebo. Maximal ST-segment depression on exercise was reduced during treatment with propranolol while treatment with the calcium ion antagonists had no significant effect. The time to the development of 1 mm ST-segment depression was prolonged by all the drugs. Nifedipine, PY-108-068 and nicardipine increased the resting heart rate whereas verapamil, diltiazem, gallopamil, KB-944, prenylamine and tiapamil produced a slight reduction. Propranolol produced a highly significant reduction in the resting and maximal heart rates and the rate-pressure product, whereas gallopamil increased the rate-pressure product by +8% and prenylamine reduced it by -10%. At the doses used, diltiazem, gallopamil and verapamil produced a greater increase in exercise tolerance than did propranolol, while the other drugs were inferior. None of the calcium ion antagonists matched the increase in the time taken to develop 1 mm ST-segment depression with propranolol, although the results with verapamil and gallopamil were close. The calcium ion antagonists are effective antianginal agents which produce their effects by mechanisms which are very different to the beta-adrenoreceptor blocking agents.
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PMID:A comparison of nine calcium ion antagonists and propranolol: exercise tolerance, heart rate and ST-segment changes in patients with chronic stable angina pectoris. 365 22

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

The effects and interactions of nifedipine and diltiazem with tubocurarine, gallamine and pancuronium and their reversal by edrophonium and neostigmine were studied on isolated skeletal muscle of the chick. The nerve-muscle preparation of the chick biventer cervicis was set up in an organ bath containing Krebs-Henseleit solution and the mechanical responses produced either by motor nerve stimulation or by drug application were recorded isometrically. The results showed that nifedipine (29-1015 microM) and diltiazem (22-572 microM) reduced, in a dose-dependent manner, the amplitude of indirectly-elicited twitch tension, evoked at 0.2 Hz with 5-10 V and 0.2 msec pulse duration, and increased the neuromuscular blockade produced by d-tubocurarine (1-254 microM), gallamine (0.01-2.0 microM) and pancuronium (0.01-7.0 microM). Edrophonium (250 nM) and neostigmine (150 nM) completely reversed the neuromuscular blockade produced by the muscle relaxants, alone and in combination with nifedipine or diltiazem. The mean IC50 values (concentrations to produce 50% of maximum inhibition) of nifedipine and diltiazem-induced depression of twitch response were 324 +/- 16 microM and 143 +/- 11 microM respectively (means +/- S.E., n = 6). Nifedipine, in high concentrations, produced small contractions (0.4 +/- 0.1 g of tension, n = 6), in the chick muscle. In contrast, diltiazem produced no such contractions in the muscle. However, in concentrations which had little effect on twitch response, diltiazem (20 microM) and nifedipine (50 microM) both increased the neuromuscular blockade produced by tubocurarine, gallamine and pancuronium by about 2-fold. Increasing the external calcium concentration, by a 2-fold, did not reverse or antagonize the inhibitory effects of diltiazem or nifedipine. It was concluded that diltiazem and nifedipine inhibit indirectly-elicited twitch tension and intensify neuromuscular blockade produced by muscle relaxants. These effects of nifedipine and diltiazem may be due to blocking influx of calcium and on release of acetylcholine from presynaptic nerve terminals.
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PMID:Interactions of nifedipine and diltiazem with muscle relaxants and reversal of neuromuscular blockade with edrophonium and neostigmine. 379 69


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