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 1,405 records · Page 78Linked to original sources
PubMed2002

Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

CONTEXT: Antihypertensive therapy is well established to reduce hypertension-related morbidity and mortality, but the optimal first-step therapy is unknown. OBJECTIVE: To determine whether treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of coronary heart disease (CHD) or other cardiovascular disease (CVD) events vs treatment with a diuretic. DESIGN: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind, active-controlled clinical trial conducted from February 1994 through March 2002. SETTING AND PARTICIPANTS: A total of 33 357 participants aged 55 years or older with hypertension and at least 1 other CHD risk factor from 623 North American centers. INTERVENTIONS: Participants were randomly assigned to receive chlorthalidone, 12.5 to 25 mg/d (n = 15 255); amlodipine, 2.5 to 10 mg/d (n = 9048); or lisinopril, 10 to 40 mg/d (n = 9054) for planned follow-up of approximately 4 to 8 years. MAIN OUTCOME MEASURES: The primary outcome was combined fatal CHD or nonfatal myocardial infarction, analyzed by intent-to-treat. Secondary outcomes were all-cause mortality, stroke, combined CHD (primary outcome, coronary revascularization, or angina with hospitalization), and combined CVD (combined CHD, stroke, treated angina without hospitalization, heart failure [HF], and peripheral arterial disease). RESULTS: Mean follow-up was 4.9 years. The primary outcome occurred in 2956 participants, with no difference between treatments. Compared with chlorthalidone (6-year rate, 11.5%), the relative risks (RRs) were 0.98 (95% CI, 0.90-1.07) for amlodipine (6-year rate, 11.3%) and 0.99 (95% CI, 0.91-1.08) for lisinopril (6-year rate, 11.4%). Likewise, all-cause mortality did not differ between groups. Five-year systolic blood pressures were significantly higher in the amlodipine (0.8 mm Hg, P =.03) and lisinopril (2 mm Hg, P<.001) groups compared with chlorthalidone, and 5-year diastolic blood pressure was significantly lower with amlodipine (0.8 mm Hg, P<.001). For amlodipine vs chlorthalidone, secondary outcomes were similar except for a higher 6-year rate of HF with amlodipine (10.2% vs 7.7%; RR, 1.38; 95% CI, 1.25-1.52). For lisinopril vs chlorthalidone, lisinopril had higher 6-year rates of combined CVD (33.3% vs 30.9%; RR, 1.10; 95% CI, 1.05-1.16); stroke (6.3% vs 5.6%; RR, 1.15; 95% CI, 1.02-1.30); and HF (8.7% vs 7.7%; RR, 1.19; 95% CI, 1.07-1.31). CONCLUSION: Thiazide-type diuretics are superior in preventing 1 or more major forms of CVD and are less expensive. They should be preferred for first-step antihypertensive therapy.

Aged↗
PubMed1994

Effects of hydrogen peroxide oxidation and calcium channel blockers on the equatorial potassium current of the frog lens.

Hydrogen peroxide, in concentrations of 10-1000 microM, produces two major changes in the current-voltage relationships associated with the equatorial potassium current of the lens. First, the resting and reversal potentials become more negative than they were prior to treatment with hydrogen peroxide and second, the membrane resistance related to the equatorial current is decreased. The shift in the resting and reversal potentials is in the opposite direction from that produced by ouabain. Based on the Nernst equation, the shift in the reversal potential suggests that there is an increase in the concentration of potassium in the lens. The 86Rb uptake and efflux are increased. These observations suggest that hydrogen peroxide stimulates the Na,K-pump. The decrease in membrane resistance is inhibited by 100 microM of quinine, a calcium-dependent potassium channel blocker, and does not decrease in a calcium-free medium. This suggests that the decrease in resistance may be secondary to an increase in lenticular calcium. These effects of hydrogen peroxide are similar to those of p-chloromercuriphenylsulfonate (pCMPS), a nearly impermeant sulfhydryl binding agent, and suggest that permeant hydrogen peroxide may increase calcium influx by acting on sulfhydryl groups on the outer surface of lens membranes. Verapamil, a calcium channel blocker, is reported to prevent cataract formation. D600, the methoxy analogue of verapamil, is a calcium channel blocker that increases the resistance associated with the equatorial current in the presence and absence of hydrogen peroxide. The gadolinium ion has a similar effect. Thus, D600 and Gd3+ partially counteract the reduction in membrane resistance produced by 50 microM hydrogen peroxide.

Animals↗
PubMed1997

Effects of an ACE inhibitor combined with a calcium channel blocker on progression of diabetic nephropathy.

It is clear that angiotensin-converting enzyme (ACE) inhibitors slow progression of diabetic nephropathy to a greater extent than other antihypertensive agents when blood pressure (BP) is reduced to levels below 140/90 mm Hg. Recent studies also demonstrate that nondihydropyridine calcium channel blockers (NDCCBs) slow progression of diabetic nephropathy in people with pre-existing renal insufficiency secondary to non-insulin dependent diabetes mellitus. The combined effects of both a CCB and ACE inhibitor have recently been examined in both animal models of diabetes as well as patients with established diabetic nephropathy. These studies demonstrate the following points: (a) at comparable BP levels, a combination of an ACE inhibitor with a NDCCB result in a greater reduction in proteinuria when compared to either components alone; and (b) conversely, addition of an ACE inhibitor to a dihydropyridine CCB (DCCB) yields effects on proteinuria similar to the ACE inhibitor alone. Therefore, addition of an ACE inhibitor to a DCCB demonstrates protection against the effects of DCCB alone. Addition of an ACE inhibitor to a NDCCB does not potentiate the preservation of renal morphology associated with progression of diabetic nephropathy when compared to either of its components alone. Conversely, a DCCB/ACE inhibitor combination yields morphologic results similar to the ACE inhibitor alone. Taken together these results suggest that ACE inhibitors when combined with a NDCCB result in greater reductions in proteinuria, and similar preservation of renal morphology when compared to either of its components alone.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2005

Effects of calcium channel blocker, mibefradil, and potassium channel opener, pinacidil, on the contractile response of mid-pregnant goat myometrium.

The present study was undertaken to investigate the in vitro influence of mibefradil, a calcium channel blocker, and pinacidil, a potassium channel opener, on pregnant goat myometrial spontaneous rhythmic contractility and contractions induced with the agonist, oxytocin. Longitudinal strips from the distal region of uterus, collected from goats at midgestation, were mounted in an organ bath for recording isometric contractions. Mibefradil (10(-8)-10(-4) M) or pinacidil (10(-10)-10(-4) M), added cumulatively to the bath at an increment of 1 log unit, caused concentration-dependent inhibition of the spontaneous rhythmic contractions of isolated uterine strips. The rhythmic contraction was, respectively, abolished at 100 and 10 microM concentrations of mibefradil and pinacidil. In a concentration-dependent manner, mibefradil (1 and 10 microM) antagonized the contractions elicited with oxytocin (10(-5)-10(-2) IU). Pretreatment of uterine strips with glibenclamide (10 microM), a selective KATP channel blocker, caused a rightward shift of the concentration-response curve of pinacidil with a concomitant decrease in its pD2 value. Pinacidil (0.3, 1 and 3 microM), in a concentration-related manner, antagonized the oxytocin (10(-5)-10(-2) IU)-induced contractile response. The inhibition of spontaneous rhythmic contractions and antagonism of oxytocin-induced contraction by mibefradil in the pregnant goat myometrium may be related to the antagonism of voltage-dependent Ca2+ channels, while by pinacidil suggests that KATP channel could be a therapeutic target for tocolysis.

Adenosine Triphosphate↗
PubMed1999

Retinitis pigmentosa: rod photoreceptor rescue by a calcium-channel blocker in the rd mouse.

Retinitis pigmentosa is an inherited degenerative disease of photoreceptors leading to blindness. A well-characterized model for this disease is provided by the retinal degeneration mouse, in which the gene for the rod cGMP phosphodiesterase is mutated, as in some affected human families. We report that D-cis-diltiazem, a calcium-channel blocker that also acts at light-sensitive cGMP-gated channels, rescued photoreceptors and preserved visual function in the retinal degeneration mouse. The long record of diltiazem prescription in cardiology should facilitate the design of clinical trials for some forms of retinitis pigmentosa.

Animals↗
PubMed1992

Benzazepinone calcium channel blockers. 2. Structure-activity and drug metabolism studies leading to potent antihypertensive agents. Comparison with benzothiazepinones.

As part of a program to discover potent antihypertensive analogues of diltiazem (3a), we prepared 1-benzazepin-2-ones (4). Benzazepinones competitively displace radiolabeled diltiazem, and show the same absolute stereochemical preferences at the calcium channel receptor protein. Derivatives of 4 containing a trifluoromethyl substituent in the fused aromatic ring show potent and long-acting antihypertensive activity. Studies of the metabolism of 4 lead to the metabolically stable antihypertensive calcium channel blockers 5a and 5c. Benzazepinone 5a is a longer acting and more potent antihypertensive agent than the second generation diltiazem analogue TA-3090 (3e).

Acetylation↗
PubMed1986

Effects of calcium channel blockers on sinoatrial conduction in the isolated and blood-perfused dog atrium.

Our previous study demonstrated that class I antiarrhythmics (fast sodium channel blockers) increased sinoatrial conduction time (SACT) in a dose-related fashion, indicating that a fast sodium current might play an important role in sinoatrial conduction. To assess a role of a slow calcium current in sinoatrial conduction, we examined effects of calcium channel blockers (diltiazem, verapamil, AQ-A 39, dilazep and bepridil) on SACT estimated by the constant atrial pacing in addition to on sinus cycle length (SCL) and on atrial developed tension (DT), using the isolated and blood-perfused dog right atrium. These calcium entry blockers except for bepridil were administered into the cannulated sinus node artery at an infusion rate of 0.2, 0.4 and 1.0 micrograms/min and bepridil at a rate of 0.6, 1.2 and 3.0 micrograms/min. The calcium antagonistic agents produced a dose-dependent decrease in DT and increase in SCL. The observed order of depression of inotropism was verapamil greater than diltiazem greater than bepridil = dilazep greater than AQ-A 39, while the order of negative chronotropism was diltiazem greater than verapamil greater than AQ-A 39 greater than dilazep greater than bepridil. However, as to dromotropism none of the five drugs exerted significant influences on SACT. From the previous and present results it is concluded that the fast sodium current may be predominantly important in sinoatrial conduction.

Animals↗
PubMed1987

Effect of a calcium channel blocker on posttraumatic spinal cord blood flow.

The normal rat spinal cord blood flow (SCBF) has been shown to increase after administration of nimodipine, a calcium channel blocker. The present study investigates the capability of nimodipine to improve SCBF, as measured by the hydrogen clearance technique, after a 53.0-gm clip compression injury to the T-1 segment of the rat spinal cord. The profound drop in mean systemic arterial blood pressure (MSAP) after cervical cord injury precluded any improvement in posttraumatic SCBF by nimodipine alone. Hence, in a randomized controlled study with five rats per group, pressor agents (whole blood, angiotensin, or adrenaline) were infused to maintain MSAP between 100 and 120 mm Hg after injury. Control animals received only a saline infusion. Nimodipine at the optimal dose found in normal animals (1.5 microgram/kg/min) was added to the pressor agents. The MSAP and other physiological parameters were measured in rats receiving the pressor agents only and in those receiving pressor agents combined with nimodipine. In rats receiving whole blood, angiotensin, or adrenaline the posttraumatic MSAP improved to between 100 and 120 mm Hg, but there was no improvement in SCBF compared to the saline group. The addition of nimodipine decreased MSAP and SCBF in all groups except those animals also receiving adrenaline, where the MSAP was maintained at 109 +/- 5 mm Hg. In these animals a significant increase in posttraumatic SCBF from 16.5 +/- 2.1 to 20.2 +/- 2.3 ml/100 gm/min (mean +/- standard error of the mean) occurred at the site of injury with the addition of nimodipine. The maintenance of an adequate MSAP by a pressor agent was crucial for nimodipine to improve posttraumatic SCBF by its ability to dilate the spinal vascular bed. Adrenaline was the only pressor agent that could fulfill the above criteria, although other pressor agents need to be investigated. Experiments are underway with the combination of adrenaline and nimodipine to further verify these encouraging results demonstrating an improvement in posttraumatic ischemia of the spinal cord.

Angiotensin II↗
PubMed1999

Calcium channel blockers in diabetic subjects: innocent at last?

Calcium antagonists are indicted as a potential trigger of a variety of complications spanning from myocardial infarction to bleeding and cancer. Three randomised controlled trials, the MIDAS, the FACET and the ABCD trial, seem to suggest that the risk for myocardial infarction is increased in diabetics on calcium antagonists. These trials in aggregate totalled only 92 cardiovascular events and it is possible that the observed differences were due to random errors. Most of the patients of the ABCD trial discontinued the medication to which they were initially randomised before the end of the study, which raised the possibility of systematic bias. In both the MIDAS and ABCD studies cardiovascular events were secondary end-points and the apparent adverse effects were identified only by subgroup analyses. Furthermore, in both studies, patients in the control groups were being treated with ACE inhibitors. The lack of a placebo group makes it impossible to establish whether the observed effects were due to the harmful influence of calcium antagonism or to the favourable effects of ACE inhibition. New data abstracted from the PIUMA database show that the rate of total cardiovascular and cardiac events did not differ between diabetics on calcium antagonists and diabetics not using these drugs. These new data are in keeping with findings in the HOT study where an impressive degree of cardiac protection was observed in diabetic patients on felodipine.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Benidipine hydrochloride--a new calcium-channel blocker of the dihydropyridine type. Pharmacokinetics, pharmacodynamics, tolerance and dose finding in mild to moderate hypertension.

(+/-)-(R*)-2,6-Dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3, 5-dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) is a newly synthetized calcium-channel blocker of the dihydropyridine type. In a phase I study with increasing single doses a statistically significant increase of the heart rate in supine and upright position as well as statistically significant decrease of the blood pressure in upright position was observed in healthy volunteers 1.5-6 h after application of 24 mg of KW-3049. Subsequently, in a placebo-controlled comparison in healthy volunteers the pulse rate in supine position increased statistically significantly on day 1 from 61.0 b/min (placebo) after application of 2 x 8 mg of KW-3049 to 67.4 b/min. After application of 2 x 10 mg of nifedipine the supine pulse rate increased to 63.3 b/min. The difference from placebo was not significant. At days 2-5 the pulse rate in upright position was always increased vs. placebo 3 h after application of KW-3049 and 1 h after application of nifedipine. As already observed in preclinical data, the mild onset of action with KW-3049 was also confirmed in these clinical phase I studies. Drug-induced effects on ergometric and psychomotoric parameters in healthy volunteers were mild, as expected, and due to aliquote dosages of 2 x 8 mg of KW-3049 and 2 x 10 mg of nifedipine only slightly different.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2005

Benidipine, a dihydropyridine-calcium channel blocker, prevents lysophosphatidylcholine-induced injury and reactive oxygen species production in human aortic endothelial cells.

Lysophosphatidylcholine (lysoPC) is a component of oxidized low-density lipoproteins (oxLDLs), which play an important role in the pathogenesis of atherosclerosis. In this study, we examined whether benidipine hydrochloride (benidipine), a dihydropyridine-calcium channel blocker with antioxidant activity, prevents lysoPC (C 16:0)-induced injury of human aortic endothelial cells (HAEC). Treatment of HAECs with lysoPC changed cell morphology, decreased cell viability and induced DNA fragmentation, leading to apoptosis. Additionally, lysoPC species containing palmitoyl (C 16:0) or stearoyl (C 18:0), which are the major components of oxLDLs, stimulated reactive oxygen species (ROS) production and induced caspase-3/7-like activity in HAECs, but lysoPC species with short acyl chains did not affect either ROS production or caspase-3/7-like activity. Pretreatment with benidipine (0.3-3 micromol/L) for 24 h protected against lysoPC-induced cytotoxicity in the endothelial cells and the drug inhibited both lysoPC-stimulated ROS production and caspase-3/7-like activation with a similar potency. Since caspase-3/7 is involved in executing the apoptotic process, the reduction of the activity of this enzyme by benedipine may explain the anti-apoptotic effect of the drug. However, benidipine did not suppress lysoPC-induced phosphorylation of mitogen-activated protein kinases and Ca2+ influx in HAECs. These results suggest that the anti-oxidant properties of benidipine may be responsible for its ability to inhibit ROS production, resulting in reduced activation of caspase-3/7. In conclusion, benidipine suppresses lysoPC-induced endothelial dysfunction through inhibition of ROS production, which is due at least in part to its antioxidant effect, and not through the inhibition of L-type voltage-dependent calcium channels.

Antioxidants↗
PubMed1994

Release of secretoneurin and noradrenaline from hypothalamic slices and its differential inhibition by calcium channel blockers.

Secretoneurin is a newly discovered peptide found in high concentrations in brain. We have studied the release of secretoneurin and noradrenaline from superfused hypothalamic slices from rat brain. Both electrical stimulation and potassium induced depolarisation released secretoneurin and noradrenaline from these slices in a calcium-dependent manner. Electrical stimulation caused a preferential release of noradrenaline when compared to the secretion elicited by high potassium. The time course of secretoneurin release was more protracted than that of noradrenaline. The calcium channel blocker omega-conotoxin inhibited only the electrically induced release of noradrenaline, whereas nifedipine inhibited only that of secretoneurin. These results establish that secretoneurin is secreted from neurons. Inhibition of this release by nifedipine is consistent with the concept that secretion from large dense core vesicles occurs at sites different from that of small vesicles and depends on calcium influx via L-type calcium channels.

Animals↗
PubMedDate not supplied

Influence of calcium channel blockers on pentylenetetrazol and electroshock-induced convulsions in mice.

Nifedipine (2.5-10 mg/kg) and verapamil (2.5 and 10 mg/kg) offered some protection against pentylenetetrazol (100 and 130 mg/kg)-induced seizure activity in mice. No protection was provided by diltiazem (1.25-10 mg/kg) in this model of experimental epilepsy. Repeated administration of calcium channel blockers (CCBs) in doses of 5 and 10 mg/kg twice daily for three days resulted in no protective effect against pentylenetetrazol. Regarding electroconvulsions, nifedipine (2.5-10 mg/kg) showed the best anticonvulsive action--for instance, in the dose of 10 mg/kg (60 min--treatment time) it elevated the threshold for electroconvulsions from 7.1 to 10.5 mA. Diltiazem (up to 10 mg/kg) and verapamil (up to 20 mg/kg) were considerably less potent in this respect. After repeated administration, only nifedipine (5-10 mg/kg) retained its protective action against electroconvulsions.

Animals↗
PubMed2002

The effects of calcium channel blockers on cardiovascular outcomes: a review of randomised controlled trials.

The choice of antihypertensive treatment should be guided by evidence of a reduction in the risk of cardiovascular (CV) events and therefore improved long-term outcome. Using pre-determined criteria, ten randomised, controlled trials that assessed the effects of calcium channel blockers (CCBs) on CV events in patients with hypertension were identified. Six of them enrolled a relatively small number (< 1500) of hypertensive patients, whereas four of the studies were much larger (> 4500 patients). The smaller studies produced mixed findings, especially those trials where CCBs were compared with diuretics; this may reflect methodological limitations and the impact of random error. The results from the four larger studies produced a consistent message: long-acting CCBs such as nifedipine, administered in a gastro-intestinal-transport-system (GITS) formulation, nitrendipine and diltiazem, reduce CV morbidity and mortality in hypertensive patients. In the one study that specifically enrolled high-risk hypertensive patients, nifedipine GITS was as effective as diuretic therapy in reducing CV events, and in all four larger studies sub-group analyses showed that the benefits of these CCBs extend to hypertensive patients with diabetes. The available evidence supports the use of these long-acting CCBs as a first-line treatment option in hypertensive patients.

Calcium Channel Blockers↗