title: Effect of amlodipine in human internal mammary artery and clinical implications.
abstract: BACKGROUND
  Graft spasm remains challenging in CABG (coronary artery bypass grafting) surgery. We investigated the inhibitory effect of a dihydropyridine calcium antagonist amlodipine on the vasoconstriction mediated by potassium chloride (KCl), human urotensin-II (hU-II), and U46619 in human internal mammary artery (IMA) from patients undergoing CABG.
  
  
  METHODS
  Isolated IMA rings (n = 78, taken from 42 patients) were studied in organ baths in two ways: the relaxing effect of amlodipine on vasoconstrictor-induced precontraction by KCl, hU-II, and U46619 and the depressing effect of amlodipine on the contraction.
  
  
  RESULTS
  Amlodipine caused full relaxation in KCl-contracted (98.0% ± 2.1%), in hU-II-contracted (98.5% ± 2.4%), and in U46619-contracted (96.3% ± 1.3%) IMA rings (n = 8) with 15.5-fold higher potency to KCl than to hU-II (effective concentration causing 50% of maximal response [EC(50)]: -8.17 ± 0.28 vs -6.98 ± 0.01 log M, p < 0.001) and 19.5-fold that to U46619 (EC(50): -8.17 ± 0.28 vs -6.88 ± 0.08 log M, p < 0.001). Pretreatment of IMA with plasma concentrations of amlodipine (-6.6 log M) significantly depressed subsequent contraction to KCl (from 20.8 ± 2.5 mN to 7.6 ± 3.0 mN, p = 0.004) and hU-II (from 14.1 ± 4.2 mN to 3.8 ± 2.0 mN, p = 0.026), but did not significantly affect the contraction to U46619.
  
  
  CONCLUSIONS
  We conclude that in human IMA amlodipine has a potent inhibitory effect on the vasoconstriction mediated by a variety of vasoconstrictors. Thus, use of amlodipine in CABG patients is favored in treating and preventing graft spasm.
authors.affiliation: TEDA International Cardiovascular Hospital, Medical College, Nankai University, Tianjin, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Bai
authors.forename: Xiao-Cheng
authors.initials: XC
authors.lastname: Liu
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Jing
authors.forename: Qin
authors.initials: Q
authors.lastname: Yang
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Tang
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 / Q000494:pharmacology; D017311:Amlodipine / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006801:Humans; D008323:Mammary Arteries / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D014579:Urotensins / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D002121:Calcium Channel Blockers; D014579:Urotensins; D014662:Vasoconstrictor Agents; D017311:Amlodipine; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C029677:urotensin II