Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Calcium Channel Blockers”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 505 records · Page 28Linked to original sources
PubMedDate not supplied

Improvement of relaxation velocity parameters by calcium channel blockers in the aging rabbit myocardium.

Normal aging in man is known to be associated with a reduction in left-ventricular diastolic function, including the rates of relaxation and filling. Calcium channel blockers have been reported to improve left-ventricular diastolic function in patients with various forms of heart disease. Clinically, the action of calcium channel blockers may be related to either a direct myocardial effect or may be secondary to the peripheral or coronary vasodilation effects. The purpose of this study is to investigate a possible direct effect of calcium channel blockers on modulation of the reported age-related reduction in myocardial relaxation. The direct effects on myocardial relaxation of the dihydropyridine calcium channel blocker, nifedipine, were studied in isolated, perfused interventricular septa and left-ventricular wall from eight young (ages 9 to 18 months) and 14 old (ages 3 to 5 years) rabbits. Septa were perfused with oxygenated Ringer's solution and paced at 48 beats/min. Maximum relaxation velocity per unit of developed tension [-dT/dt]/T, and relaxation time per unit of developed tension tR/T were continuously measured before and after infusion of calcium channel blockers. In absence of drugs, the older rabbits demonstrated a mean [-dT/dt]/T which was 32% lower (p < 0.003) and a mean tR/T which was 45% higher (p < 0.005) than the younger rabbits. When nifedipine was introduced at concentrations > 10(-8) M equivalent to doses above the therapeutic free-plasma concentration in humans, all contraction and relaxation parameters were depressed. However, at lower doses, equivalent to doses in the clinical therapeutic range, [-dT/dt]/T was increased in the older rabbit septa by 18% in the presence of nifedipine. tR/T was shortened in the older rabbit septa by 17% in the presence of nifedipine. Myocardial relaxation in older rabbits after drug infusion approximated these parameters in the younger rabbits prior to drug infusion (P = NS). Calcium channel blockers had similar beneficial effects on the relaxation properties of the myocardium in younger rabbits. All beneficial effects were observed at concentrations of calcium channel blockers which were within and below the clinically therapeutic range of plasma free drug concentration, i.e., 5 x 10(-9) to 4 x 10(-8) M. Potential differences in relaxation effects related to different segments of the myocardium and different mechanical recording vectors were evaluated. Isolated left ventricle preparations from aging rabbits demonstrated improvements in tR/T and [-dT/dt]/T similar to those observed in the septum. Furthermore, improvement in mechanical function along the y-axis and x-axis vectors of the septum was similar.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed2001

Calcium channel blockers, postural vasoconstriction and dependent oedema in essential hypertension.

Treatment with calcium channel blocker (CCB)s, dihydropyridines and others, is frequently complicated by dependent oedema in the absence of sodium retention or cardiac failure, a bothersome side effect of unclear aetiology. The present paper reviews our own and other work dealing with the antagonism exerted by such drugs on postural vasoconstriction, a mechanism triggered by limb venous congestion during orthostasis and controlled through a local sympathetic axo-axonic reflex and increased myogenic tone in response to changes in transmural pressure. By stabilising capillary pressure, postural vasoconstriction counteracts fluid hyperfiltration consequent to gravitational stimuli, and consistent evidence shows attenuation of this response by L-type calcium channel blockers. Interference with the postural reflex control of skin blood flow may therefore contribute to dependent oedema, although cannot entirely explain its development. Attenuation of postural vasoconstriction may amplify the fluid hyperfiltration induced by CCBs through other mechanisms, such as imbalanced intracapillary pressure or enhanced vascular permeability, which are the main factors determining net fluid filtration into the interstitial compartment.

Calcium Channel Blockers↗
PubMed1994

Dopaminergic function in rat brain after oral administration of calcium-channel blockers or haloperidol. A microdialysis study.

Microdialysis technique was used to study the effects of both acute and repeated oral administration of calcium-channel blockers (flunarizine, cinnarizine, verapamil, nifedipine and nicardipine) in dopaminergic function in rat brain and to compare them to the effects of haloperidol. Acute flunarizine, nicardipine or haloperidol increased extracellular levels of dopamine (DA) or metabolites. After repeated (18 days) administration, nicardipine, nifedipine, verapamil or haloperidol increased and flunarizine decreased extracellular striatal levels of dopamine or metabolites. Chronic treatment with calcium-channel blockers or haloperidol failed to block K(+)-evoked release of dopamine. This suggests that the calcium-channel blockers used in this study do not influence calcium entry necessary for DA release. An acute challenge with haloperidol caused either no change or a decrease in extracellular levels of DA or metabolites after repeated administration of calcium-channel blockers or haloperidol. This is considered to be due to the lesser response of dopaminergic neurons because of treatment. A neuroleptic-like mechanism of action together with a decrease in firing activity and/or a reduced dopamine re-uptake of dopaminergic neurons are considered.

Action Potentials↗
PubMed1982

Inhibition of bronchoconstriction in the guinea pig by a calcium channel blocker, nifedipine.

We investigated the inhibitory effects of nifedipine, a calcium channel blocker, on airway smooth muscle constriction in the guinea pig. In vitro, nifedipine (0.003 to 3.0 microM) caused significant dose-dependent reversal of intrinsically existing tone in both tracheal spirals and parenchymal strips. Nifedipine also inhibited the constriction of tracheal spirals and parenchymal strips induced by two different agonists, histamine and carbachol. At a concentration of 3.0 microM, nifedipine increased by 48-fold the concentration of carbachol required to produce a 50% of maximal contraction of parenchymal strips, and by 5-fold the concentration of histamine. Increasing extracellular calcium ion concentration in the tissue baths significantly diminished the inhibitory action of nifedipine. In vivo, nifedipine (30 micrograms/kg body weight given intravenously) did not alter pulmonary resistance or dynamic compliance. It did, however, attenuate histamine-induced bronchoconstriction in 3 of 5 animals studied. In response to the maximal dose of histamine infused, mean pulmonary resistance rose 40 +/- 16% (SEM) after nifedipine versus 182 +/- 65% in the control animals (p less than 0.025) and mean dynamic compliance decreased 35 +/- 8% after nifedipine versus 58 +/- 6% in the control animals (p less than 0.01). Thus, this calcium channel blocker inhibits mediator-induced constriction of both central and peripheral airway contractile tissues, a finding of potential clinical applicability.

Animals↗
PubMed2006

Nifedipine inhibits picrotoxin-induced seizure activity: further evidence on the involvement of L-type calcium channel blockers in epilepsy.

A large body of evidence supports the role of L-type calcium channels in epileptogenesis. The aim of the present study was to study the efficacy of the specific L-type calcium channel blocker nifedipine on seizure activity induced by picrotoxin (PTX). Adult female Sprague-Dawley rats were used in these experiments. The intraperitoneal administration of nifedipine (5 mg/kg) did not significantly alter the latency to onset of clonic seizure induced by intraperitoneal injection of PTX (4 mg/kg). Higher doses of the drug (10 and 20 mg/kg) significantly increased the latency of onset of clonic seizure in a dose-dependent manner. Nifedipine (10 mg/kg) did not reduce the incidence of clonic seizures in the animals injected with PTX, but inhibited tonic seizure and the progression of clonic seizures into maximal tonic seizures in four of eight of the animals. The drug (20 mg/kg) inhibited clonic seizure in four of six of the animals and abolished minimal or maximal tonic seizures in all the animals. In conclusion, our study provides further evidence on the antiepileptic effect of L-type calcium channel blocker nifedipine by showing its protective effect on seizure activity induced by PTX.

Animals↗
PubMed1985

Differential inhibition of bronchoconstriction by the calcium channel blockers, verapamil and nifedipine.

Recent studies have demonstrated that the calcium channel blocking agents can inhibit experimentally induced bronchoconstriction in asthmatics, but their protective action has been variable. To clarify the influence of stimulus intensity and choice of calcium blocker on these reported differences in outcome, we performed noncumulative thermal stimulus-response curves using isocapnic hyperventilation of cold air in 8 asthmatics. Subjects received pretreatment with orally administered nifedipine (20 mg), intravenously administered verapamil (10 mg bolus followed by a continuous infusion), or appropriate placebos in a randomized, double-blind fashion. Verapamil afforded no consistent protection against the thermal challenges, whereas nifedipine significantly blunted the bronchoconstrictor response to stimuli of low (p less than 0.02) and middle (p less than 0.03) intensity. At the highest thermal burden, the effect of nifedipine was inconsistent and not significantly different from that of placebo. These results indicate that the protection from bronchoconstriction afforded by the calcium channel blockers depends on the choice of agent and the intensity of the bronchoconstricting stimulus, and they raise the possibility that the contribution of transmembrane calcium ion influx to the pathogenesis of bronchoconstriction may vary according to stimulus intensity.

Adult↗
PubMed1991

Cytoprotective effects of calcium channel blockers. Mechanisms and potential applications in hepatocellular injury.

Deregulation of calcium homeostasis is strongly implicated in the development of cellular injury, including in hepatocytes, and is thought to be the limiting step in transition to an irreversible stage. Calcium channel blockers appear to exert their cytoprotective effects through several mechanisms. These may involve blockade of L-(long-lasting)-type calcium channels, reduction of oxidative stress, antagonism at inflammatory mediator receptor sites and interaction at other intracellular sites. Studies relating to the liver are few but suggest that calcium channel blockers may have a role to play in limiting hepatocellular damage, especially those arising from exposure to a variety of toxic agents.

Animals↗
PubMed1994

Effects of the calcium channel blockers, diltiazem and Ro 40-5967, on systemic haemodynamics and plasma noradrenaline levels in conscious dogs with pacing-induced heart failure.

1. Calcium channel blockers increase cardiovascular morbidity and mortality in patients with left ventricular dysfunction. These adverse effects are probably related to the negative inotropic effect of calcium channel blockers and/or a neurohormonal activation. 2. The present study was designed to examine, in conscious dogs, the acute haemodynamic and sympathetic effects of diltiazem and Ro 40-5967 (a novel calcium channel blocker) in the control state and in heart failure. 3. Thirteen dogs were instrumented with a micromanometer and an aortic catheter. After completion of experiments in the control state, heart failure was induced by right ventricular pacing (250 beats min-1, 3 weeks). Diltiazem and Ro 40-5967 were given intravenously (0.8 mg kg-1 and 1.0 mg kg-1 respectively). Cardiac output was measured by a thermodilution technique. 4. In the control state, both agents decreased similarly mean aortic pressure with significant increases in heart rate, cardiac output (both +1.0 l min-1 and P < 0.001) and plasma noradrenaline (both +55%) without changes in left ventricular dP/dtmax. In heart failure, for matched decreases in mean aortic pressure, neither diltiazem nor Ro 40-5967 changed heart rate significantly; diltiazem decreased cardiac output (-0.3 l min-1, P < 0.02) and dP/dtmax (-14%, P < 0.001) while Ro 40-5967 still increased cardiac output (+0.3 l min-1, P < 0.02) although the increased amount was smaller than in the control state. Plasma noradrenaline level was increased more during diltiazem infusion (+120%) than during Ro 40-5967 infusion (+38%, P < 0.001). 5. Diltiazem and Ro 40-5967 have similar haemodynamic and sympathetic effects in the control state.Heart failure alters haemodynamic and sympathetic responses to both calcium channel blockers but the magnitude of the alteration appears to be different. Diltiazem exerts a depressant effect on cardiac function which cannot be overcome by its vasodilator effect and sympathetic stimulation, while Ro 40-5967 has little effect on cardiac function. These data suggest that novel calcium channel blockers with less depressant effect may not be detrimental in heart failure.

Animals↗
PubMed1990

Calcium channel blockers in affective illness: role of sodium-calcium exchange.

Available evidence suggests that verapamil and perhaps other calcium channel blockers are effective in treating mania but not unipolar depression. This article briefly reviews the clinical experience and reexamines potential mechanisms. It is proposed that antimanic efficacy is primarily related to inhibition of sodium-calcium counterexchange rather than calcium channel blockade.

Bipolar Disorder↗
PubMed1986

Ineffectiveness of organic calcium channel blockers in antagonizing long-term potentiation.

Evidence has accumulated suggesting that the presence of calcium is critical for development of hippocampal long-term potentiation (LTP). However, there is a paucity of information about whether calcium's role in LTP is pre- or postsynaptic. In the present study, we examined the effectiveness of nitrendipine, verapamil, flunarizine and the benzodiazepine diazepam in: blocking voltage-dependent calcium channels; blocking synaptic transmission; and preventing development of LTP. Using the in vitro slice preparation, we obtained intracellular and extracellular recordings from guinea pig hippocampal CA1 pyramidal cells. At the cellular level, all 4 drugs were ineffective in blocking voltage-dependent calcium spikes (TTX resistant) and the calcium-dependent afterhyperpolarization. Verapamil and diazepam appeared to antagonize synaptic transmission, as reflected in smaller population spike amplitudes. Development of long-term potentiation was not affected by the presence of verapamil, flunarizine and diazepam. Nitrendipine appeared to reduce the percentage of slices exhibiting LTP; however, ethanol, the vehicle used to dissolve nitrendipine, was shown in separate experiments to reduce the percentage of slices exhibiting LTP. These results suggest that neither the organic calcium channel blockers--nitrendipine, verapamil, and flunarizine--nor micromolar concentrations of diazepam are potent blockers of extrasynaptic voltage-sensitive calcium channels in hippocampus. They thus cannot be used to demonstrate a specific pre- or postsynaptic calcium role in LTP.

Action Potentials↗
PubMed1987

Comparative effects of calcium-channel blockers and beta-adrenergic blocker on early diastolic time intervals and A-wave ratio in patients with hypertrophic cardiomyopathy.

To compare the effects of calcium-channel blockers with those of beta-adrenergic blockers in patients with hypertrophic cardiomyopathy (HCM), diastolic time intervals (IIA-O time, from the second heart sound to the O point of apexcardiogram, IIA-MVO time, from IIA to the mitral valve opening, and MVO-O time, from the MVO to the O point of apexcardiogram), and A-wave ratio measured from apexcardiogram were evaluated before and after more than three months of treatment. In both groups, heart rate significantly decreased after treatment. The IIA-MVO time was not affected by either drug. The IIA-O and the MVO-O times were significantly shortened by calcium-channel blockers (from 234.6 +/- 77.4 ms to 204.6 +/- 39.2 ms; p less than 0.01, and from 133.1 +/- 66.4 ms to 100.3 +/- 34.0 ms; p less than 0.01, respectively). However, they were not affected by beta-adrenergic blocker. A-wave ratio significantly decreased after calcium-channel blockers (from 18.0 +/- 9.8% to 13.7 +/- 7.3%; p less than 0.01) and beta-adrenergic blocker (from 21.7 +/- 12.6% to 17.2 +/- 8.0%; p less than 0.01). From these observations, it is suggested tht calcium-channel blockers improved the early diastolic filling rate, whereas beta-adrenergic blocker did not affect it. It is concluded that the effects of calcium-channel blockers and beta-adrengergic blocker on early diastolic time intervals were different in patients with HCM.

Adrenergic beta-Antagonists↗
PubMed1997

Calcium channel blockers correct in vitro mitochondrial toxicity of cellulose acetate.

We studied the action of rinse solutions from cellulose acetate hemodialyzers on isolated mitochondria. We showed that concentrates from the rinses impaired the adenosine 5'-triphosphate (ATP) synthesis as reflected by the decrease in respiration during state 3 and in P/O ratio. This impairment results from a calcium release from mitochondria that is induced by rinse solution concentrates. The release, triggering the mitochondrial calcium carrier, would explain the decrease in ATP synthesis. Moreover, rinse solution concentrates hinder mitochondrial calcium storage. The rise in cytosolic calcium in hemodialyzed patients may be related, at least in part, to these findings, since a lack of ATP impairs the ATP-dependent cellular calcium-extrusion pumps. We also showed that calcium channel blockers, at therapeutically relevant doses, restore ATP synthesis and calcium storage in mitochondria impaired by rinse solution concentrates. Finally, these in vitro results were confirmed by experiments on cells in culture proving that Diltiazem counteracts the cytotoxicity of rinse solution concentrates. These findings are consistent with observations that these drugs suppress the increase in leukocyte cytosolic calcium in dialyzed patients. Moreover, this would help explain the efficiency of calcium channel blockers in cells without L-calcium channels.

Animals↗
PubMed1995

Is the beneficial effect of calcium channel blockers against cyclosporine A toxicity related to a restoration of ATP synthesis?

ATP synthesis inhibited by Cyclosporine A is restored by calcium channel blockers: nifedipine, verapamil, bepridil, diltiazem. ATP synthesis was estimated using liver mitochondria by measuring the rate of respiration during state 3 and a measure of the yield of ATP synthesis, the P/O ratio. The study of calcium fluxes through mitochondrial membrane indicates that calcium channel blockers counteract the mitochondrial calcium storage induced by cyclosporine A. If the restoration of ATP synthesis observed in vitro also occurred in vivo, the increase in ATP pool might contribute to a better functioning of the Ca2+ extrusion pumps of the cells, thereby maintaining the cytosolic calcium concentration (Cai), in the normal range. The nephrotoxicity of cyclosporine A appears to be due to a vasoconstrictive effect related to an increased Cai. This result may account for the reduction of clinical cyclosporine A toxicity by calcium channel blockers. Verapamil appears to be the most efficient in restoring ATP synthesis.

Adenosine Triphosphate↗
PubMed1991

Chronic use of the calcium channel blocker nifedipine has no significant effect on bone metabolism in men.

Calcium channel blockers have been reported to have such diverse effects on reduction in protein synthesis, diminished incorporation of proline into new collagen, and decreased hormone release in vitro. The chronic affect of the calcium channel blocker nifedipine was examined in vivo to determine the possible impact of pharmacologic calcium channel blockade on bone metabolism. Eleven Caucasian males treated with an average of 40 mg/d nifedipine for an average of three years were compared to 11 control males matched for age, height, weight, activity level, cardiovascular status, and calcium intake. No significant differences between groups were noted in bone mineral density at the lumbar spine (L2-4), proximal femur (femoral neck, Ward's triangle and trochanter), and proximal and distal radius. There were also no significant differences in parameters of bone turnover (alkaline phosphatase, osteocalcin, urine calcium/creatinine, and hydroxyproline/creatinine ratio), or hormones that might affect calcium metabolism and bone (testosterone, PTH, 25(OH) vitamin D, and calcitonin). In summary, chronic nifedipine use in males is not associated with either a beneficial or adverse effect on bone metabolism.

Adult↗
PubMed1988

2-(2-Aryl-2-oxoethylidene)-1,2,3,4-tetrahydropyridines. Novel isomers of 1,4-dihydropyridine calcium channel blockers.

The title compounds are novel double bond isomers of 1,4-dihydropyridine-type calcium channel blockers (CCB). These derivatives were prepared by using the Hantzsch dihydropyridine synthesis. The assignment of structure was based on spectroscopic data and a regiochemically unambiguous synthesis. Several of the analogues inhibited [3H]nitrendipine binding with IC50 values as low as 25 nM. By comparison, nifedipine, a clinically useful 1,4-dihydropyridine CCB, inhibits [3H]nitrendipine binding with an IC50 of 1.6 nM. In the Langendorff rat heart preparation, treatment with the more potent derivatives produced marked dose-related increases in coronary flow with little or no effect on heart rate or contractility, except at the highest concentrations tested. The selectivity for vascular versus cardiac effects was similar to that of nifedipine, i.e., the concentration producing vasodilation was approximately 2 orders of magnitude lower than the concentration eliciting cardiodepression. These novel isomers extend the structure-activity relationships for calcium channel blockers into a series closely related to the 1,4-dihydropyridines.

Animals↗
PubMed1991

Calcium channel blockers modulate airway constriction in the canine lung periphery.

We studied the effect of two voltage-sensitive calcium channel blockers on Na2EDTA-induced bronchoconstriction in the canine lung periphery. A wedged bronchoscope technique was used to measure collateral system resistance before and after challenges with aerosolized Na2EDTA, hypocapnia, aerosolized acetylcholine, and increased flow of dry air in anesthetized mongrel dogs. Nifedipine, a dihydropyridine calcium channel blocker, reduced hypocapnia-induced bronchoconstriction by 88 +/- 6% (SE) but did not alter Na2EDTA-induced constriction. Verapamil, a phenylalkylamine calcium channel blocker, attenuated hypocapnia- and Na2EDTA-induced bronchoconstriction by 69 +/- 6 and 44 +/- 7%, respectively, but did not significantly alter responses to either acetylcholine or dry air challenge. We conclude that calcium influx through voltage-sensitive calcium channels, perhaps of the T subtype, has a limited role in the initiation of Na2EDTA-induced bronchoconstriction in the canine lung periphery.

Acetylcholine↗
PubMedDate not supplied

Anticonvulsant effects of calcium channel blockers in partial and generalized model epilepsies.

The calcium channel blockers D890 and verapamil reduced neuronal calcium currents in single snail neurons with intra- and extracellular applications, respectively. Epileptic discharges of single neurons in the rat's motor cortex (in vivo) were depressed in amplitude by intracellular injection of D890. Focal seizure discharges and generalized tonic-clonic seizure activity in the cerebral cortex of the rat were reduced by intracerebroventricular perfusion of verapamil. In non-epileptic rats verapamil failed to exert a depressive effect on somatosensory evoked potentials and on the waves of the spontaneous EEG.

Animals↗
PubMed2006

Neuroprotective effect of calcium channel blocker against retinal ganglion cell damage under hypoxia.

The purpose of this study was to determine whether iganidipine, nimodipine and lomerizine, potentially useful calcium channel blockers for ophthalmic treatment, have direct retinal neuroprotective effects against hypoxic damage in experimental in vitro model. We used purified retinal ganglion cells (RGCs) from newborn rats. RGCs were incubated in controlled-atmosphere incubator in which oxygen levels were reduced to 5% normal partial pressure and cell viability was assessed. We also examined the effect of calcium channel blockers on the calcium ion concentration in RGC under hypoxic stress by calcium imaging. Iganidipine, nimodipine and lomerizine (0.01-1 microM) increased the RGC viability. Increase in intra-RGC calcium ion concentration by hypoxic damage was reduced by these calcium channel blockers. In conclusion, iganidipine, nimodipine and lomerizine were effective against hypoxic RGC damage in vitro. This neuroprotective effect was thought to be mediated by blocking calcium ion influx into RGC. These findings suggest that iganidipine, nimodipine and lomerizine have a direct neuroprotective effect against RGC damage related to hypoxia.

Analysis of Variance↗