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

The combination of a beta-adrenoceptor-blocking drug with the dihydropyridine calcium channel antagonist, nitrendipine, has particular therapeutic advantages in the management of hypertension. The beta-blocker reduces any reflex increases in sympathetic nervous system and renin-angiotensin system activity that result from the vasodilating action of nitrendipine, whereas the latter drug reduces the peripheral effects of beta-blockade. At least three clinical studies have documented additional hypotensive effects when nitrendipine is used in combination with beta-blockers in the treatment of hypertension. This therapeutic combination is well tolerated, produces minimal alterations in clinical laboratory tests, and does not produce significant depression of atrioventricular conduction or left ventricular function.
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PMID:Combination therapy of hypertension with beta-adrenoceptor blockers and the calcium channel antagonist nitrendipine. 246 80

1. Post-rest inotropy in canine ventricular myocardium has proved a useful indicator of sarcoplasmic reticular calcium release. This phenomenon is converted to rest depression by the calcium channel activator (agonist), Bay K 8644 as well as other chemically diverse agents such as caffeine and ryanodine. 2. Rapid cooling contractures and post-rest contraction amplitude were used as independent measures of sarcoplasmic reticular calcium content and release. Simultaneous recordings of transmembrane action potentials and their accompanying contractions were obtained to determine the association between electrophysiological and mechanical events. The present study was designed to elucidate the mechanism by which Bay K 8644, caffeine and ryanodine alter force production after variable periods of rest. 3. Bay K 8644 (1 microM) increased steady state contraction in response to a constant train of stimulation, caused rest-depression after 2 and 8 min rest, prolonged action potential duration and increased action potential plateau amplitude. Augmented steady state tension was not accompanied by any change in time to peak tension or rapid cooling contracture amplitude. However, the post-rest rapid cooling contracture was greatly diminished compared to that observed prior to Bay K 8644 treatment. 4. Caffeine (3 and 5 mM) caused rest-depression with an increase in steady state contraction amplitude. Along with this there was a slight decrease in action potential duration and plateau amplitude and an increase in time to peak tension. The rapid cooling contractures were virtually abolished at all conditioning intervals. The effect of caffeine on twitch tension and cooling contracture is consistent with the ability of this compound to inhibit calcium sequestration by the sarcoplasmic reticulum. 5. A combination of Bay K 8644 and caffeine caused significantly less rest-depression than that seen with Bay K 8644 alone. The augmented twitch tension was accompanied by a long time to peak tension and action potential duration. However, there was no increase in the amplitude of the rapid cooling contracture, either after a regular train of stimulation or after rest, compared to that seen after Bay K 8644. 6. Ryanodine (10 nM), produced rest-depression, reduced steady state twitch tension and augmented the rest-depression produced by Bay K 8644. The steady state rapid cooling contracture remained unchanged when both agents were present simultaneously, while the post-rest rapid cooling contracture was significantly depressed compared to that observed with Bay K 8644 alone. 7. Bay K 8644 and ryanodine appear to have similar actions with respect to promoting diastolic loss of calcium from the sarcoplasmic reticulum. Although caffeine also decreases post-rest potentiation, it antagonizes rest-depression caused by Bay K 8644. The data from these experiments suggest that this reversal is a result of depressed intracellular calcium buffering and enhanced myofilament sensitivity produced by caffeine in the presence of increased transmembrane calcium influx promoted by Bay K 8644.
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PMID:Effects of caffeine and ryanodine on depression of post-rest tension development produced by Bay K 8644 in canine ventricular muscle. 247 6

The effect of ischemia on the function of cardiac sarcoplasmic reticulum (SR) was assessed by the calcium uptake rate of rat whole-heart homogenates in the presence of 10 mM oxalate. Previous studies have shown that this uptake is restricted to the SR. The contribution of the ryanodine-sensitive fractions of the SR to the total homogenate uptake was assessed by using 20 microM ruthenium red and 625 microM ryanodine to close the SR calcium release channel under previously established optimal conditions. Global ischemia of 10, 15, 30, and 60 minutes depressed homogenate calcium uptake rate 19 +/- 2%, 50 +/- 6%, 65 +/- 3%, and 81 +/- 5%, respectively. This decrease was not observed when the uptake rates were measured after closure of the calcium channel with ryanodine or ruthenium red. Similar results were obtained with a Langendorff in vitro perfusion preparation, in which calcium uptake was decreased 35 +/- 5%, 37 +/- 8%, 58 +/- 7%, and 64 +/- 4% after 10, 15, 30, and 60 minutes of ischemia, but no significant decrease was observed when homogenate uptake rates were measured in the presence of ryanodine. Thus, ischemia caused a depression in the calcium uptake rate of cardiac SR only when this activity was measured in the absence of SR calcium channel blockers. Reperfusion of ischemic hearts in a Langendorff preparation resulted in recovery of homogenate calcium uptake activity that correlated well with the return to sinus rhythm of the reperfused hearts. These reperfused hearts showed no change in the calcium uptake rate measured in the presence of ryanodine. These results suggest that the decrease in homogenate calcium uptake caused by ischemia is not due to a defect in calcium pumping capabilities but is due to an increased efflux through the ryanodine-sensitive calcium release channel of cardiac SR.
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PMID:Differential effect of global ischemia on the ryanodine-sensitive and ryanodine-insensitive calcium uptake of cardiac sarcoplasmic reticulum. 247 12

The ability of the dihydropyridine calcium channel activators, (-)-S-BAY K 8644 and (+)-S-202-791 and the calcium channel inhibitor, (+)-R-BAY K 8644, to modify the differential deglutitive actions of glutamate and muscarine at premotor loci in the nucleus tractus solitarii was investigated in urethane-anaesthetised rats. At subnuclei ventralis and intermedialis loci, pneumophoretic application (20-100 pl) from multibarrelled glass micropipettes (tip diameter 2-5 microns) of glutamate (10-20 pmol) evoked aminophosphonovaleric acid (APV)-insensitive pharyngeal swallows; at sites in the subnucleus centralis of the nucleus tractus solitarii glutamate evoked an APV-sensitive single-wave oesophageal response, whereas muscarine (5-10 pmol) evoked rhythmic oesophageal contractions. Both (-)-S-BAY K 8644 and (+)-S-202-791, applied in prepulses of 10-20 fmol and 100-200 fmol, respectively, either had no effect or selectively and reversibly enhanced or inhibited the glutamate-evoked responses. Identical results were obtained by intravenous administration of (-)-S-BAY K 8644 (10-50 micrograms/kg). Micropneumophoretic (20-50 fmol) or intravenous (10-50 micrograms/kg) administration of (+)-R-BAY K 8644 suppressed the N-methyl-D-aspartate (NMDA)-mediated oesophageal responses in a reversible and selective manner. The dihydropyridine vehicle produced a transient depression of all types of deglutitive responses. It is concluded that, within the deglutitive subnuclei of the nucleus tractus solitarii, "L"-type voltage-operated calcium channels are associated with NMDA-receptor-mediated deglutitive mechanisms. The inhibition or a lack of effect produced by the dihydropyridine calcium channel activators is explained in part by their actions at other sites e.g. release of inhibitory transmitters.
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PMID:Modulation of solitarial deglutitive N-methyl-D-aspartate receptors by dihydropyridines. 247 24

In 15 patients with coronary heart disease (mean data: age 60.4 years, body-weight average 72.5 kg, four females, eleven males, six patients with myocardial infarction) the long-term treatment with verapamil (340 mg/die p.o.) was replaced by gallopamil (123 mg/die). In six patients the additional treatment with long-lasting nitrates was continued. During a period of 1 year symptom-limited exercise tests (bicycle ergometry) were performed repeatedly (baseline, 1, 3, 6, and 12 months later). In comparison to the pretreatment with verapamil the calcium channel blocker gallopamil proved to be equally effective on the overall exercise performance, heart rate, and blood pressure regulation. Parameters of myocardial ischemia (maximal ST-depression, onset of significant ST-depression, duration of ST-changes after cessation of work) are less evident. Minor side effects include prolongation of the PQ-interval (0.24 on the mean in five patients) and arterial hypotension (two patients). One patient underwent coronary artery surgery as the complaints of angina pectoris worsened.
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PMID:[Exercise capacity of coronary heart disease patients in long-term follow-up with gallopamil in comparison with premedication with verapamil]. 251 57

The effects of crotoxin, the neurotoxin of the venom of the South American rattlesnake (Crotalus durissus terrificus), was studied by using the myenteric plexus-longitudinal muscle preparation of the guinea pig ileum. Crotoxin (0.02-4.0 microM) caused depression of the twitch response of the electrically stimulated preparation. This transitory depression depended on the concentration of crotoxin; since crotoxin diminished the output of acetylcholine, this depression may be due to the inhibition of the release of acetylcholine from the plexus. Crotoxin also induced an early contraction, followed by relaxation; as the contraction was inhibited by aspirin and indomethacin, it may have resulted from the release of prostaglandin. In addition, a late persistent contracture was observed after the early contraction. The contracture was resistant to blockage by muscarinic, histamine and serotonin antagonists, to hexamethonium, a non-depolarizing ganglionic blocking substance and to tetrodotoxin, a sodium channel blocker. The contracture was blocked by an elevated concentration of calcium (10 mM) and by verapamil, a calcium channel blocker.
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PMID:The effect of crotoxin on the longitudinal muscle-myenteric plexus preparation of the guinea pig ileum. 254 13

1. Excitatory postsynaptic potentials (e.p.s.ps) were recorded from the submandibular parasympathetic ganglia of newborn rats (10-20 days old), by intracellular microelectrode recording and a suction electrode to deliver stimulus trains to the lingual nerve (15 stimuli at 0.1, 0.3, 1, 3, and 10 Hz, 22 degrees C). Only evoked responses without voltage-dependent action potentials were analyzed (observed at membrane potentials negative to -70 mV), and e.p.s.p. amplitudes were determined for the plateau responses during each train (5-15th response). 2. Cadmium, an inorganic calcium channel antagonist, reduced e.p.s.p. amplitudes in a dose-dependent manner (Kd 74 microM, P less than 0.01). Nickel (1-300 microM) did not attenuate the amplitude of evoked responses. 3. Verapamil (0.1-30 microM), a phenylamine, had no significant effects upon e.p.s.p. amplitudes at any frequency examined. Higher concentrations of verapamil (100 microM) blocked neurally evoked responses in a manner consistent with the antagonism of voltage-sensitive sodium currents. 4. Diltiazem, a benzothiazepine, reduced e.p.s.p. amplitudes in a dose-dependent manner, the depression being accentuated at high stimulation frequencies (80% block at 30 microM and 10 Hz). The pure (-)-cis enantiomer of diltiazem (10-30 microM) was without effect. 5. Amlodipine, a 1,4-dihydropyridine, did not antagonize synaptic transmission at any stimulus frequency examined (10-30 microM, 0.1-10 Hz, n = 3). 6. Amiloride, a potassium-sparing diuretic, depressed the amplitudes of evoked responses in a dose-dependent manner (one-site Kd 31 microM, P less than 0.005), although the extent of the block was alleviated with high stimulus frequencies. The effects of 30 microM amiloride were unlikely to be of post-synaptic origin as both the amplitudes of miniature e.p.s.ps, and the iontophoretic potentials induced by exogenous acetylcholine, were not attenuated by treatment with this compound. The amiloride derivative, 3',4'-dichlorobenzamil was ineffective in reducing the amplitude of e.p.s.ps (30-100 microM). 7. omega-Conotoxin GVIA, a marine neurotoxin, which depressed whole cell calcium currents recorded from cultured rat parasympathetic cardiac neurones (up to 90% block at 10 nM), was ineffective at blocking synaptic transmission in submandibular ganglia (0.1-1 microM). 8. The differential effects of these calcium channel antagonists upon synaptic transmission in rat parasympathetic ganglia, suggest that either more than one type of calcium channel may be involved in transmitter release, or that the presynaptic calcium channels possess pharmacological sensitivities different from those of channel types described in ne
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PMID:Inhibition of neurally-evoked transmitter release by calcium channel antagonists in rat parasympathetic ganglia. 257 81

We investigated the effect of cardiovascular depression on the pressor responses to the alpha 1-adrenoceptor selective agonist methoxamine, and the alpha 2-adrenoceptor selective agonist B-HT 920 in anesthetized ganglion-blocked rats. The calcium channel blocking drug nifedipine preferentially inhibited the effect of B-HT 920, as has been reported by other authors. Lowering the starting blood pressure by hemorrhage, by nitroprusside infusion, or by additional pentobarbitone also preferentially inhibited the pressor effect of B-HT 920. These selective effects of vascular depression on B-HT 920 are consistent with predicted interactions between functional antagonists and a partial (low-efficacy) agonist. This was tested in part by reducing the maximum effect of methoxamine by phenoxybenzamine treatment. Under these conditions, methoxamine behaved like B-HT 920 in that it was sensitive to inhibition by nitroprusside infusion. By analogy, the vasodepressive effect of calcium channel blocking drugs could be responsible for the preferential inhibition of the vasoconstrictor responses to alpha 2-adrenoceptor agonists. It is concluded that a differential reliance on influx of extracellular Ca2+ by alpha 1- and alpha 2-adrenoceptors may not be the only explanation of the selective effect of calcium channel blocking drugs.
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PMID:Alpha 1- and alpha 2-adrenoceptor-mediated pressor responses: are they differentiated by calcium antagonists or by functional antagonism? 258 Oct 97

Pretreatment with the calcium channel-blocking agent verapamil lowers the coronary flow associated with the first rise in myocardial extracellular potassium [( K+]e). The mechanisms underlying this effect are unclear. It is not known whether this effect is a manifestation of verapamil-induced reduction in baseline cardiac work before the reduction in coronary flow, is dependent on a selective depression of contractility within the low-flow region, or is independent of an effect on myocardial work. This study was performed to determine the relations between changes in regional contractility and [K+]e before and after verapamil (0.2 mg/kg followed by 6.5 micrograms/kg/min) when left anterior descending (LAD) coronary flow is progressively reduced and when verapamil-induced alterations in baseline myocardial work are prevented by atrial pacing and by dobutamine (4.3 +/- 2.2 micrograms/kg/min) to maintain systemic arterial blood pressure and contractility. Before verapamil-dobutamine, myocardial [K+]e rose and regional contractility fell when LAD coronary flow was reduced to 87.7 +/- 9.6% and 83.4 +/- 7.4%, respectively, of the unrestricted control value (p = NS). After verapamil-dobutamine, the threshold flow for rise in [K+]e decreased to 56.4 +/- 13.5% of the unrestricted control flow (p = 0.003), but the threshold flow for regional contractility fall was unchanged (84.8 +/- 11.3%). Our results indicate that the protective effect of verapamil on preventing ischemia-induced [K+]e release is not dependent on a reduction in baseline myocardial work. In this setting, calcium channel blockade by verapamil results in a dissociation between the ionic and mechanical events that occur when coronary flow is reduced.
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PMID:Metabolic protection by verapamil during graded coronary flow reduction independent of effect on baseline systolic function. Separation of mechanical and ionic markers of ischemia. 259 43

Nisoldipine is a new calcium channel blocker of the dihydropyridine family with a high affinity for coronary vessels. We assessed the efficacy of nisoldipine in the treatment of asymptomatic ischemia in 12 patients with chronic, stable angina. Two to four weeks of daily therapy with prn nitroglycerin and placebo was followed by 24-hour ambulatory electrocardiographic recording for ST segment assessment. After two weeks of once-daily nisoldipine, 10 to 20 mg, the ambulatory recording was repeated. A significant difference was seen in ischemia-magnitude products of asymptomatic ischemic episodes in placebo versus active drug periods (P less than .05). When total ischemic burden was considered (ST segment depression during both painless and painful episodes), the difference was even more significant (P less than .02).
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PMID:Silent myocardial ischemia: improvement with nisoldipine therapy. 264 67


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