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L-type Calcium Channel Blocker (l-type + calcium_channel_blocker)

Distribution by Scientific Domains
Medical Sciences100%

Selected Abstracts

Nifedipine enhances cGMP production through the activation of soluble guanylyl cyclase in rat ventricular papillary muscle

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2005
Kazuhiko Seya
It is known that nifedipine, an L-type calcium channel blocker, increases cGMP production, which partially contributes to the relaxation of vascular smooth muscle. The aim of our investigation was to clarify whether or not nifedipine regulates cGMP production, which has a physiological role in cardiac muscle. To measure contractile responses and tissue cGMP levels, left ventricular papillary muscles prepared from male Wistar rats (350,400 g) were mounted in the isolated organ chamber under isometric conditions and electrically paced by means of platinum punctate electrodes (1 Hz, 1 ms duration). In papillary muscle preparation, the negative inotropic effect induced by nifedipine (30 to 300 nm) was significantly inhibited in the presence of ODQ (1H-[1,2,4]oxidazolo[4,3-a]quinoxaline-1-one; 10 ,m), a soluble guanylyl cyclase inhibitor. Furthermore, nifedipine (100 nm) strongly increased the tissue cGMP level, which was significantly decreased in the presence of ODQ. On the other hand, NG -monomethyl-l-arginine (100 ,m), a nitric oxide synthase inhibitor, did not inhibit either the negative inotropic effect or cGMP production induced by nifedipine. These results indicate that in rat left ventricular papillary muscle, nifedipine augments its negative inotropic effect at least partly through direct activation of cardiac soluble guanylyl cyclase but not nitric oxide synthase. [source]

Anti-apoptotic effect of benidipine, a long-lasting vasodilating calcium antagonist, in ischaemic/reperfused myocardial cells

BRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2001
Feng Gao
Ischaemia/reperfusion causes intracellular calcium overloading in cardiac cells. Administration of calcium antagonists reduces myocardial infarct size. Recent in vitro studies have demonstrated that calcium plays a critical role in the signal transduction pathway leading to apoptosis. However, whether or not calcium antagonists may reduce myocardial apoptosis induced by ischaemia-reperfusion, and thus decrease myocardial infarction, has not been directly investigated. The present study investigated the effects of benidipine, an L-type calcium channel blocker, on myocardial infarct size, apoptosis, necrosis and cardiac functional recovery in rabbits subjected to myocardial ischaemia/reperfusion (MI/R, 45 min/240 min). Ten minutes prior to coronary occlusion, rabbits were treated with vehicle or benidipine (10 ,g kg,1 or 3 ,g kg,1, i.v.). In the vehicle-treated group, MI/R caused cardiomyocyte apoptosis as evidenced by DNA ladder formation and TUNEL positive nuclear staining (12.2±1.1%). Treatment with 10 ,g kg,1 benidipine lowered blood pressure, decreased myocardial apoptosis (6.2±0.8%, P<0.01 vs vehicle) and necrosis, reduced infarct size (20±2.3% vs 49±2.6%, P<0.01), and improved cardiac functional recovery after reperfusion. Administering benidipine at 3 ,g kg,1, a dose at which no haemodynamic effect was observed, also exerted significant anti-apoptosis effects, which were not significantly different from those observed with higher dose benidipine treatment. However, treatment with this low dose benidipine failed to reduce myocardial necrosis. These results demonstrate that benidipine, a calcium antagonist, exerts significant anti-apoptosis effects, which are independent of haemodynamic changes. Administration of benidipine at a higher dose produced favourable haemodynamic effects and provided additional protection against myocardial necrotic injury and further improved cardiac functional recovery. British Journal of Pharmacology (2001) 132, 869,878; doi:10.1038/sj.bjp.0703881 [source]

L-type calcium channel blockers and Parkinson disease in Denmark

ANNALS OF NEUROLOGY, Issue 5 2010
Beate Ritz MD
Objective This study was undertaken to investigate L-type calcium channel blockers of the dihydropyridine class for association with Parkinson disease (PD), because some of these drugs traverse the blood,brain barrier, are potentially neuroprotective, and have previously been evaluated for impact on PD risk. Methods We identified 1,931 patients with a first-time diagnosis for PD between 2001 and 2006 as reported in the Danish national hospital/outpatient database and density matched them by birth year and sex to 9,651 controls from the population register. The index date for cases and their corresponding controls was advanced to the date of first recorded prescription for anti-Parkinson drugs, if prior to first PD diagnosis in the hospital records. Prescriptions were determined from the national pharmacy database. In our primary analyses, we excluded all calcium channel blocker prescriptions 2 years before index date/PD diagnosis. Results Employing logistic regression analysis adjusting for age, sex, diagnosis of chronic pulmonary obstructive disorder, and Charlson comorbidity score, we found that subjects prescribed dihydropyridines (excludes amlodipine) between 1995 and 2 years prior to the index date were less likely to develop PD (odds ratio, 0.73; 95% confidence interval, 0.54,0.97); this 27% risk reduction did not differ with length or intensity of use. Risk estimates were close to null for the peripherally acting drug amlodipine and for other antihypertensive medications. Interpretation Our data suggest a potential neuroprotective role for centrally acting L-type calcium channel blockers of the dihydropyridine class in PD that should be further investigated in studies that can distinguish between types of L-type channel blockers. ANN NEUROL 2010;67:600,606 [source]