title: Inhibition of vasoconstriction by AJ-2615, a novel calcium antagonist with alpha(1)-adrenergic receptor blocking activity in human conduit arteries used as bypass grafts.
abstract: OBJECTIVE
  Graft spasm may develop during coronary artery bypass grafting and reversal of spasm is still challenging. The purpose of this study was to investigate the in vitro vascular relaxant properties of AJ-2615 in human internal mammary artery (IMA).
  
  
  METHODS
  We studied 264 IMA rings taken from 65 patients undergoing coronary artery bypass grafting surgery with organ bath technique. The interaction between AJ-2615 and various vasoconstrictors was investigated in two ways.
  
  
  RESULTS
  AJ-2615 caused complete relaxation in methoxamine-contracted IMA rings (100.0+/-0.0%; n = 8) and nearly full relaxation in potassium chloride-contracted IMA rings (91.4+/-5.7%; n = 8) or noradrenaline-contracted IMA rings (89.3+/-2.8%; n = 8). AJ-2615 also induced remarkable relaxation in IMA rings contracted by other vasoconstrictors. In comparison with the alpha1-adrenoceptor antagonist prazosin, AJ 2615 showed similar maximal relaxation in IMA rings contracted by methoxamine or norepinephrine. On the other hand, incubation with AJ-2615 (0.1-1 microM) significantly inhibited all the vasoconstrictor-mediated vasoconstriction except endothelin-1 in a concentration-dependent manner.
  
  
  CONCLUSIONS
  The results suggested that in human IMA, AJ-2615 has an inhibitory effect on vasoconstriction mediated by a variety of vasoconstrictors and the mechanism of relaxation may be related to its calcium antagonism and alpha1-adrenergic receptor blocking activity. AJ-2615 may have important clinical implications for patients undergoing coronary artery bypass surgery for reversing and preventing graft spasm.
authors.affiliation: Cardiovascular Research, Providence Heart Institute & Albert Starr Academic Center, Providence St Vincent Hospital, Portland, OR, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Liu
authors.forename: S H
authors.initials: SH
authors.lastname: Floten
authors.forename: Q
authors.initials: Q
authors.lastname: Yang
authors.forename: G W
authors.initials: GW
authors.lastname: He
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000368:Aged; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D001026:Coronary Artery Bypass; D003988:Dibenzothiepins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects* / Q000502:physiology; D008729:Methoxamine / Q000494:pharmacology; D008875:Middle Aged; D009638:Norepinephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D002121:Calcium Channel Blockers; D003988:Dibenzothiepins; D019332:Endothelin-1; D010879:Piperazines; D014662:Vasoconstrictor Agents; D012701:Serotonin; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D008729:Methoxamine; C067818:monatepil; D009638:Norepinephrine; D011224:Prazosin