title: Inhibition of vasoconstriction by potassium channel opener aprikalim in human conduit arteries used as bypass grafts.
abstract: OBJECTIVE
  Potassium channel openers (KCOs) are of potential therapeutic value. Little is known about the effect of these drugs on human conduit arteries used as coronary bypass grafts. The purpose of this study was to determine the effect of the KCO aprikalim (RP52891) on human arteries used as coronary bypass grafts with emphasis on the possible difference in the inhibitory effect on depolarizing agent-mediated rather than receptor-mediated contraction.
  
  
  METHODS
  Human internal mammary artery segments (IMA, n = 88) taken from 28 patients were studied. Concentration-relaxation curves for aprikalim were established in IMA precontracted with three vasoconstrictors (K+, U46619, and phenylephrine). In IMA rings incubated with aprikalim (1 or 30 microM) for 10 min concentration-contraction curves for the three vasoconstrictors were constructed.
  
  
  RESULTS
  Aprikalim-induced relaxation was less in K+ (37.3 +/- 6.4%) than in U46619 (80.2 +/- 7.7%, P=0.002), or phenylephrine (67.5 +/- 7.0%, P=0.038) -precontracted IMA. The EC50 for K+-(-5.40 +/- 0.12 log M) was significantly higher than that for phenylephrine (-6.43 +/- 0.30 log M, P=0.007) but not significant compared with that for U46619 (-5.81 +/- 0.11, P>0.05). Pretreatment with aprikalim depressed the contraction by phenylephrine from 140.6 +/- 27.6% to 49.3 +/- 14.1% (P=0.002) and shifted the EC50 11.0-fold higher in rings treated with 1 microM aprikalim (P=0.007). Treatment of aprikalim did not significantly reduce the K+ and U46619-induced contraction (P>0.05) but shifted the concentration-contraction curves rightward (2.8-fold higher for K+, P<0.05 and 2.2-fold higher for U46619, P<0.05).
  
  
  CONCLUSIONS
  This study demonstrates that aprikalim has vasorelaxant effects in human conduit arteries used as coronary artery bypass grafts contracted by a variety of vasoconstrictors and this effect is vasoconstrictor-selective with greater potency for alpha1-adrenoceptor agonists than for depolarizing agent K+. These findings provide information on the possible use of this KCO in various clinical settings.
authors.affiliation: Grantham Hospital, Department of Surgery, University of Hong Kong, Hong Kong.
authors.forename: G W
authors.initials: GW
authors.lastname: He
authors.forename: C Q
authors.initials: CQ
authors.lastname: Yang
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D001026:Coronary Artery Bypass; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects* / Q000502:physiology; D008875:Middle Aged; D010656:Phenylephrine / Q000494:pharmacology; D010847:Picolines / Q000494:pharmacology*; D015221:Potassium Channels / Q000819:agonists*; D011714:Pyrans / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D010847:Picolines; D015221:Potassium Channels; D011714:Pyrans; D014665:Vasodilator Agents; D010656:Phenylephrine; C061043:aprikalim; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid