The Annals of thoracic surgery · 2015
Effect of Benidipine in Human Internal Mammary Artery and Clinical Implications.
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Hou Hai-Tao, Wang Jun, Wang Zheng-Qing, Liu Xiao-Cheng, Marinko Marija, Novakovic Aleksandra, Yang Qin, He Guo-Wei
Аннотация
BACKGROUND: Graft spasm remains challenging in coronary artery bypass grafting (CABG). Calcium antagonists are commonly used in patients with coronary artery disease. This study investigated the inhibitory effect of third-generation dihydropyridine calcium channel antagonist benidipine on the vasoconstriction induced by various vasoconstrictors in the human internal mammary artery (IMA).
METHODS: Isolated human IMA rings (N = 65, taken from 37 patients undergoing CABG) were studied in a myograph in 2 ways: the relaxing effect of benidipine on vasoconstrictor-induced precontraction by KCl and U46619 and the depressing effect of benidipine at plasma concentrations on the contraction. Enzyme-linked immunosorbent assay (ELISA) was used to measure the change of the protein related to the L-type calcium channel.
RESULTS: Benidipine caused more relaxation in KCl-contracted (86.7% ± 3.3%; n = 12) than in U46619-contracted (63.8% ± 5.3%; n = 8; p < 0.001) IMA rings. Pretreatment of IMA with plasma concentrations of benidipine (-6.92 log M) significantly depressed subsequent contraction by KCl (from 17.3 ± 2.7 mN to 7.4 ± 1.2 mN; n = 6; p < 0.05) but did not significantly affect the contraction caused by U46619. Benidipine also caused a decrease of caveolin (CaV)1.2 protein content (0.55 ± 0.02 versus 0.63 ± 0.02 mg/mL; p < 0.05).
CONCLUSIONS: We conclude that in human IMA, the third-generation dihydropyridine calcium channel antagonist benidipine has a potent inhibitory effect on the vasoconstriction mediated by a variety of vasoconstrictors. Use of benidipine in patients undergoing CABG may provide vasorelaxant or antispastic effects in the grafts.
METHODS: Isolated human IMA rings (N = 65, taken from 37 patients undergoing CABG) were studied in a myograph in 2 ways: the relaxing effect of benidipine on vasoconstrictor-induced precontraction by KCl and U46619 and the depressing effect of benidipine at plasma concentrations on the contraction. Enzyme-linked immunosorbent assay (ELISA) was used to measure the change of the protein related to the L-type calcium channel.
RESULTS: Benidipine caused more relaxation in KCl-contracted (86.7% ± 3.3%; n = 12) than in U46619-contracted (63.8% ± 5.3%; n = 8; p < 0.001) IMA rings. Pretreatment of IMA with plasma concentrations of benidipine (-6.92 log M) significantly depressed subsequent contraction by KCl (from 17.3 ± 2.7 mN to 7.4 ± 1.2 mN; n = 6; p < 0.05) but did not significantly affect the contraction caused by U46619. Benidipine also caused a decrease of caveolin (CaV)1.2 protein content (0.55 ± 0.02 versus 0.63 ± 0.02 mg/mL; p < 0.05).
CONCLUSIONS: We conclude that in human IMA, the third-generation dihydropyridine calcium channel antagonist benidipine has a potent inhibitory effect on the vasoconstriction mediated by a variety of vasoconstrictors. Use of benidipine in patients undergoing CABG may provide vasorelaxant or antispastic effects in the grafts.
Предметные рубрики MeSH
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic AcidCalcium Channel BlockersCalcium Channels, L-TypeDihydropyridinesDose-Response Relationship, DrugDrug Evaluation, PreclinicalEnzyme-Linked Immunosorbent AssayHumansIn Vitro TechniquesMammary ArteriesMyographyPotassium ChlorideVasoconstrictionVasoconstrictor AgentsVasodilator Agents