title: Vasorelaxation induced by new third-generation dihydropyridine calcium antagonist azelnidipine in human internal mammary artery.
abstract: BACKGROUND
  Graft spasm remains challenging in coronary artery bypass graft (CABG) surgery. Calcium antagonists are commonly used in patients with coronary artery disease. We investigated the inhibitory effect of the new third-generation dihydropyridine calcium antagonist azelnidipine on the vasoconstriction in human internal mammary artery (IMA) from patients undergoing CABG.
  
  
  METHODS
  Isolated IMA rings (n = 68, taken from 28 patients) were studied in myograph in two ways: the relaxing effect of azelnidipine on vasoconstrictor-induced precontraction by potassium chloride (KCl) and U46619; and the depressing effect of azelnidipine at plasma concentrations on the contraction.
  
  
  RESULTS
  Azelnidipine caused full relaxation in KCl-contracted (96.5% ± 0.7%) and in U46619-contracted (96.5% ± 1.4%) IMA rings (n = 8), with 28.8-fold higher potency to KCl than to U46619 (EC50 -7.49 ± 0.21 versus -6.03 ± 0.11 log M, p < 0.01). Pretreatment of IMA with plasma concentrations of azelnidipine (-6.1 log M) significantly depressed subsequent contraction to KCl (from 25.8 ± 2.2 mN to 16.0 ± 1.5 mN, p < 0.01) and U46619 (from 30.6 ± 4.0 mN to 16.5 ± 2.2 mN, p < 0.05).
  
  
  CONCLUSIONS
  We conclude that in human IMA, azelnidipine has a potent inhibitory effect on the vasoconstriction mediated by a variety of vasoconstrictors. Thus, use of azelnidipine in CABG patients is favored for treating and preventing graft spasm.
authors.affiliation: TEDA International Cardiovascular Hospital, Medical College, Nankai University, Tianjin, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Gao
authors.affiliation: TEDA International Cardiovascular Hospital, Medical College, Nankai University, Tianjin, China.
authors.forename: Xiao-Cheng
authors.initials: XC
authors.lastname: Liu
authors.affiliation: TEDA International Cardiovascular Hospital, Medical College, Nankai University, Tianjin, China.
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Jing
authors.affiliation: TEDA International Cardiovascular Hospital, Medical College, Nankai University, Tianjin, China; Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yang
authors.affiliation: TEDA International Cardiovascular Hospital, Medical College, Nankai University, Tianjin, 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: D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D001026:Coronary Artery Bypass; D004095:Dihydropyridines / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects* / Q000502:physiology*; D008875:Middle Aged; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D001383:Azetidinecarboxylic Acid; C061679:azelnidipine
keywords: 23