title: Effect of Benidipine in Human Internal Mammary Artery and Clinical Implications.
abstract: 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.
authors.affiliation: Center for Basic Medical Research and Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Tianjin, China; The Affiliated Hospital of Hangzhou Normal University and Zhejiang University, Hangzhou, China.
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Hou
authors.affiliation: Center for Basic Medical Research and Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Tianjin, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Center for Basic Medical Research and Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Tianjin, China.
authors.forename: Zheng-Qing
authors.initials: ZQ
authors.lastname: Wang
authors.affiliation: Center for Basic Medical Research and Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Tianjin, China.
authors.forename: Xiao-Cheng
authors.initials: XC
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
authors.forename: Marija
authors.initials: M
authors.lastname: Marinko
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Novakovic
authors.affiliation: Center for Basic Medical Research and Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Tianjin, China; The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Center for Basic Medical Research and Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Tianjin, China; The Affiliated Hospital of Hangzhou Normal University and Zhejiang University, Hangzhou, China; Department of Surgery, Oregon Health and Science University, Portland, Oregon. Electronic address: gwhezj@163.com.
authors.forename: Guo-Wei
authors.initials: GW
authors.lastname: He
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000032:analysis / Q000187:drug effects; D004095:Dihydropyridines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D066298:In Vitro Techniques; D008323:Mammary Arteries / Q000187:drug effects*; D009213:Myography; D011189:Potassium Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines; C419385:L-type calcium channel alpha(1C); D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C061004:benidipine; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid