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Anti-apoptotic effect of benidipine, a long-lasting vasodilating calcium antagonist, in ischaemic/reperfused myocardial cells.
Br J Pharmacol. 2001 Feb; 132(4):869-78.BJ

Abstract

1. 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. 2. 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 microg x kg(-1) or 3 microg x kg(-1), i.v.). 3. 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 microg x 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 microg x 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. 4. 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.

Authors+Show Affiliations

Division of Emergency Medicine, Thomas Jefferson University, 1020 Sansom Street, Philadelphia, Pennsylvania 19107, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11181428

Citation

Gao, F, et al. "Anti-apoptotic Effect of Benidipine, a Long-lasting Vasodilating Calcium Antagonist, in Ischaemic/reperfused Myocardial Cells." British Journal of Pharmacology, vol. 132, no. 4, 2001, pp. 869-78.
Gao F, Gong B, Christopher TA, et al. Anti-apoptotic effect of benidipine, a long-lasting vasodilating calcium antagonist, in ischaemic/reperfused myocardial cells. Br J Pharmacol. 2001;132(4):869-78.
Gao, F., Gong, B., Christopher, T. A., Lopez, B. L., Karasawa, A., & Ma, X. L. (2001). Anti-apoptotic effect of benidipine, a long-lasting vasodilating calcium antagonist, in ischaemic/reperfused myocardial cells. British Journal of Pharmacology, 132(4), 869-78.
Gao F, et al. Anti-apoptotic Effect of Benidipine, a Long-lasting Vasodilating Calcium Antagonist, in Ischaemic/reperfused Myocardial Cells. Br J Pharmacol. 2001;132(4):869-78. PubMed PMID: 11181428.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anti-apoptotic effect of benidipine, a long-lasting vasodilating calcium antagonist, in ischaemic/reperfused myocardial cells. AU - Gao,F, AU - Gong,B, AU - Christopher,T A, AU - Lopez,B L, AU - Karasawa,A, AU - Ma,X L, PY - 2001/2/22/pubmed PY - 2001/5/1/medline PY - 2001/2/22/entrez SP - 869 EP - 78 JF - British journal of pharmacology JO - Br J Pharmacol VL - 132 IS - 4 N2 - 1. 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. 2. 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 microg x kg(-1) or 3 microg x kg(-1), i.v.). 3. 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 microg x 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 microg x 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. 4. 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. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/11181428/Anti_apoptotic_effect_of_benidipine_a_long_lasting_vasodilating_calcium_antagonist_in_ischaemic/reperfused_myocardial_cells_ L2 - https://doi.org/10.1038/sj.bjp.0703881 DB - PRIME DP - Unbound Medicine ER -