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

Ouabain induces oscillatory afterpotentials (OAPs) in organ-cultured young (3 day old) embryonic chick hearts. Since increased [Ca]i resulting from an inhibition of the Na pump by ouabain triggers oscillatory movements of Ca2+ (i.e. OAPs) intracellularly, Ca2+ influx through the cell membrane, which tends to increase [Ca]i, may be important in developing the OAPs. Therefore, in the present experiments, effects of calcium channel blockers on ouabain-induced OAPs in organ-cultured 3 day old embryonic chick hearts were examined. Automaticity was suppressed by elevating [K]o to 6 mM. To induce the OAPs, the preparations were stimulated (0.5 Hz) in the presence of ouabain (2.5-6.3 microM). The calcium channel blockers (10 microM) depressed the OAPs in the following order of potency: bepridil greater than verapamil greater than nifedipine greater than diltiazem. This order of potency of the calcium channel blockers in depressing the OAPs was the same as that for drug penetration into the cells, but different from that for depressing slow action potentials: nifedipine greater than diltiazem greater than verapamil greater than bepridil (our previous findings). These results suggest that an intracellular site of action of the calcium channel blockers is important for depression of the OAPs, and suppression of the slow inward Ca2+ current cannot be the sole mechanism for suppression of the OAPs by these drugs.
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PMID:Effects of calcium channel blockers on ouabain-induced oscillatory afterpotentials in organ-cultured young embryonic chick hearts. 242 Jun 19

The effects of local anesthetics in depressing myocardial contractility were studied in isolated guinea pig right ventricular papillary muscles. Bupivacaine and etidocaine, 4 and 10 microM, showed reverse frequency-dependent depression of contractility, that is, less significant depression of contractility at higher stimulation frequencies (2-3 Hz) than at lesser frequencies (less than 1 Hz). Lidocaine, 40 microM, demonstrated a similar trend. In contrast, the normal action potential maximum rate of depolarization (Vmax), a measure of sodium channel conductance, was significantly more depressed at 2-3 Hz by bupivacaine and etidocaine than by lidocaine. Consequently, contractile depression could be overcome only at higher stimulation frequencies, at which conduction was depressed. To explore the mechanism of the contractile depression, local anesthetic effects were studied on slow (calcium channel-mediated) action potentials in partially depolarized papillary muscles. Etidocaine and bupivacaine, 4 and 10 microM, and lidocaine, 40 and 100 microM, caused a marked depression of the late-peaking contractile responses, attributed to Ca2+ release from the sarcoplasmic reticulum. In contrast, only 10 microM bupivacaine caused any significant depression of the slow action potential rate of depolarization (to 89% of control), consistent with a possible small depression of Ca2+ entry.
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PMID:Depression of myocardial contractility in vitro by bupivacaine, etidocaine, and lidocaine. 242 88

Effects of pentobarbital on the calcium current of Aplysia neurons were investigated under current- and voltage-clamp conditions using the conventional two-microelectrode technique. Pentobarbital attenuated the progressive broadening of repeated action potentials of somata, suggesting a reduction in the calcium current. When calcium ion was replaced with barium ion in the perfusing solution, in which neither sodium nor potassium ions carried transmembrane currents, the barium current (IBa) which flowed through the calcium channel of the cell membrane was generated by depolarizing pulses of several hundred milliseconds applied every 1 min from a holding potential of -50 mV. The IBa was not affected by tetrodotoxin (30 microM). The current was decreased by pentobarbital (0.1-5 mM) in a dose-dependent manner. The inhibition was much greater at a lower pH of the perfusate, indicating that the uncharged form of the agent was responsible. The voltage-dependent inactivation of the IBa proceeded with two time constants [190 +/- 21 and 2020 +/- 146 msec (N = 4) at -10 mV], both of which were shortened by adding 1 mM pentobarbital [to 120 +/- 18 and 540 +/- 51 msec (N = 4), respectively]. The IBa recovered from the inactivation with two time constants [60 +/- 7 and 871 +/- 76 msec (N = 3) at -50 mV]. The anesthetic (1 mM) prolonged both of them, to 124 +/- 20 and 1480 +/- 172 msec (N = 3), respectively, resulting in a use-dependent depression of the current at 2-Hz stimulation. Pentobarbital reduced the IBa to a greater extent when the holding potential was more positive (-30 instead of -50 mV), indicating a higher affinity of the drug to the inactivated state of the channel. These findings suggest that the attenuation of the progressive broadening of successive spikes by pentobarbital is due to a decrease in the voltage- and time-dependent calcium current, ending in depression of transmitter release from the nerve terminal.
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PMID:Reduction of the voltage-dependent calcium current in Aplysia neurons by pentobarbital. 243 43

Cholinergic and monoaminergic hypotheses have dominated affective disorders research. The propriety of an hypothesis is determined by the point of a field in its development. Both categories of hypotheses have encouraged important research but their utility can be limited by the assumption that the pathophysiology of depression and mania is due to cholinergic or monoaminergic pathology. In actuality, neurotransmitter networks interact and are mutually regulating. The cholinergic-monoaminergic interaction theory (CMIT) is a dynamic account of the mutual inter- and intra-regulation of cholinergic, noradrenergic, dopaminergic and serotonergic systems in the pathophysiology of affective disorders. This model maintains that virtually every variable related to the neurobiology of bipolar disorder is regulated by mechanisms internal and external to those neurotransmitter systems involved in its pathophysiology. In principle, these variables include receptor density and sensitivity, membrane properties, cytosolic calcium, magnesium and sodium ion concentrations, activities of ATPases and calcium channel gating and cascade mechanisms. This array of variables stems from the assumption that the brain is a complex, unified dynanism. The CMIT posits homeostatic mechanisms preserving the direction of this dynanism. In this article, the theme of neurotransmitter-neurotransmitter system interaction is developed and the CMIT is offered as a paradigm useful in addressing the pathophysiology of affective disease from within the conceptual framework of a neurotransmitter system interaction theory.
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PMID:Cholinergic-monoaminergic interaction in the pathophysiology of the affective disorders? 243 81

The role of the endothelium in contraction and relaxation produced by the dihydropyridine calcium channel modulators was examined in porcine coronary smooth muscle. The optically pure dihydropyridine calcium agonists (+)-S202-791 and (-)-Bay k 8644 both produced greater contractions in tissues without endothelium compared with tissues with intact endothelium. In contrast, histamine produced the same degree of contraction in tissues with and without endothelium. In the presence of KCl-induced active muscle tone, the optically pure calcium antagonists (-)-R202-791 and (+)-Bay k 8644 and the nitrovasodilator isosorbide dinitrate all produced the same degree of relaxation in tissues with and without endothelium. These results suggest that the endothelium plays an inhibitory role in dihydropyridine-induced contraction. When coronary rings with intact endothelium were pretreated for 60 min with 10 or 100 nM (-)-R202-791, the contraction to subsequent addition of (+)-S202-791 was significantly greater than in control tissues pretreated with only solvent. However, in rings with denuded endothelium, pretreatment with (-)-R202-791 resulted in a rightward shift of the dose-response curve to (+)-S202-791, and a depression of the maximal contraction compared with controls. Thus, the interaction between the calcium agonist [(+)-S202-791] and antagonist [(-)-R202-791] is more complex than competitive inhibition. We suggest that the calcium agonists produce two effects, a release of endothelium-derived relaxant factor and a direct contraction of smooth muscle; the calcium antagonists can inhibit both processes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A possible role for the endothelium in porcine coronary smooth muscle responses to dihydropyridine calcium channel modulators. 243 89

The effect of racemic disopyramide and its enantiomers on the action potential was studied in Tyrodes (4.0 mM KCL)-superfused canine cardiac Purkinje fibers. Nonstereodependent depression of action potential amplitude and phase 0 Vmax was observed in control fibers and following pretreatment with either nisoldipine or verapamil. Stereospecific effects of the enantiomers were prominent during repolarization phases of the action potential and could be modified by pretreatment with the calcium channel blocking agents. R(-) disopyramide decreased action potential duration at 90% repolarization and shortened the effective refractory period. S(+) disopyramide increased action potential duration at 90% repolarization and prolonged refractoriness. This disparate effect of the enantiomers was eliminated following pretreatment with verapamil. Stereospecific effects on repolarization persisted when fibers were pretreated with nisoldipine, a more selective calcium channel blocking agent that lacks effects on outward plateau current. The data suggest that the increase in action potential duration and refractoriness produced by disopyramide is mediated by a stereospecific inhibition of outward repolarizing current by the S(+) enantiomer.
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PMID:Stereospecific effects of disopyramide enantiomers following pretreatment of canine cardiac Purkinje fibers with verapamil and nisoldipine. 243 93

Since the cardinal hemodynamic disorder in essential hypertension is an increased total peripheral resistance, drugs that can lower resistance without reducing blood flow would be particularly useful. The calcium antagonists seem to fulfill this criterion. The purpose of this work was to study the hemodynamic effects at rest and during exercise of three calcium channel blockers, verapamil, nifedipine, and nisoldipine, in patients with mild to moderate essential hypertension. Fifty-four patients aged 20-64 years with pretreatment diastolic blood pressures of between 95 and 120 mm Hg were studied at rest and during exercise on an ergometer bicycle. Blood pressure was recorded intraarterially and cardiac output was measured by Cardiogreen. After the initial study, 10 patients were treated with verapamil (40-80 mg three times daily), 15 with nifedipine (long-acting form, 20-80 mg daily), and 19 with nisoldipine (10-40 mg daily). After 1 year the hemodynamic study was repeated. The immediate response to the first dose was studied in the patients taking nisoldipine and in 10 patients after taking placebo tablets. Placebo induced no significant changes in central hemodynamics during the first 3 h after tablet intake. The calcium antagonists induced a reduction in blood pressure and in total peripheral resistance (in the order of 10-18%) without any reduction in cardiac index. Reflex tachycardia and an increase in cardiac output were seen in the first 2 h after the first dose of nisoldipine, but after 1 year the heart rate was unchanged compared with the pretreatment rate at rest and during exercise. In contrast, heart rate was reduced on verapamil treatment, particularly during exercise (about 10% of patients), but this was compensated for by an increase in the stroke volume. The hemodynamic profiles of the three calcium channel blockers were slightly different, especially with respect to the heart rate response. Total peripheral resistance was reduced, acutely as well as chronically, and no depression in cardiac pump function was seen, either at rest or during exercise.
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PMID:Central hemodynamic changes of calcium antagonists at rest and during exercise in essential hypertension. 244 6

The objective of the present study was to determine the time-courses for depression and recovery of calcium-mediated action potentials in canine Purkinje fibers following exposure to dihydropyridine (DHP) calcium channel antagonists and to determine if the reported discrepancy (up to 1,000 X) between I50 values for inducing physiologic effects in isolated tissues and the dissociation constant (Kd) for [3H]nitrendipine binding to membrane sites could be reduced when physiologic measurements were made under experimentally determined steady-state conditions. Changes in dV/dtmax of slow calcium-mediated action potentials (20 mM KCl, 10(-6) M isoproterenol) were recorded at 10-min intervals during exposure (2-4 h) to nifedipine, nitrendipine, and PY 108-068 (10(-9) M-4 X 10(-8) M). Time to steady state was slow, with half-life t1/2 values of 40 min (nifedipine), 84 min (nitrendipine), and 81 min (PY 108-068). Steady state I50 values for depressing dV/dtmax were 12.08 (nifedipine), 5.74 (nitrendipine), and 4.88 nM (PY 108-068). In isolated cardiac sarcolemma preparations (37 degrees C), these compounds competed for [3H]nitrendipine binding sites with Ki values of 8.1, 1.3, and 4.9 nM, respectively. These results show that attainment of steady-state depression of calcium channel function can be slow, but that the discrepancy between the physiologic data and the binding data is reduced significantly (less than 5 X) when physiologic measurements are made at steady state and binding studies are performed at 37 degrees C.
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PMID:Relationship between steady-state depression of calcium-dependent action potentials and competition for binding sites by nifedipine, nitrendipine, and PY 108-068. 245 Feb 42

Four cases are reported in which substantial depression was associated with the use of the calcium channel blocker nifedipine. In one instance, a patient became unresponsive to treatment with nortriptyline when nifedipine was introduced. In each case, the depression resolved following discontinuation of nifedipine. Possible mechanisms by which nifedipine may influence affective states are discussed.
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PMID:Depression associated with nifedipine-induced calcium channel blockade. 245 83

To examine the antianginal and antihypertensive efficacy of nitrendipine, a new calcium channel blocking agent, 25 patients with chronic stable angina pectoris (NYHA I-III) and systemic hypertension underwent cardiac catheterization and treadmill exercise tests. Acute hemodynamic results were obtained before and 2 h after oral administration of 20 mg nitrendipine. They showed a significant decrease in aortic pressure (162.1 +/- 27.4/80.0 +/- 12.1 vs. 134.9 +/- 23.5/74.2 +/- 13.1 mm Hg), pulmonary arterial pressure (25.4 +/- 5.4/11.3 +/- 3.7 vs. 21.9 +/- 5.4/9.9 +/- 3.7 mm Hg), and pulmonary wedge pressure (10.0 +/- 4.4 vs. 6.6 +/- 3.8 mm Hg). Cardiac index (+31%) and stroke volume (+33%) increased markedly, whereas heart rate remained unchanged (66.9 +/- 11.4 vs. 66.8 +/- 10.8 beats/min). Chronic hemodynamic results and exercise tolerance tests were obtained before and 8 weeks after oral nitrendipine therapy. A significant decrease in arterial blood pressure was observed (167 +/- 22/86 +/- 10 vs. 126 +/- 32/76 +/- 19 mm Hg). Exercise tolerance improved concerning test duration (+22%) and total exercise capacity (+37%). Maximal ST-segment depression decreased by 30% (0.2 +/- 0.03 vs. 0.14 +/- 0.02 mV) and subsequently the anginal frequency was reduced from 7.8 +/- 2.1 to 3.8 +/- 1.7 attacks/week (-50%). The maximal rate-pressure product during exercise remained unchanged. Plasma levels of cholesterol, triglycerides, and LDL- and HDL-cholesterol did not show any significant alterations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute and chronic effects of nitrendipine on hemodynamics and myocardial ischemia in patients with combined angina pectoris and hypertension. 246 68


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