title: Interaction between vasodilators and vasopressin in internal mammary artery and clinical significance.
abstract: BACKGROUND
  Arginine vasopressin (AVP) has recently been demonstrated as an alternative in the treatment of severe refractory vasodilatation in coronary artery bypass grafting. However, AVP may be a spasmogen for graft spasm. We compared the in vitro antispastic effect among calcium-channel antagonists (nifedipine, diltiazem, and verapamil), nitroglycerin, and the highly selective AVP (V1) receptor antagonist [1-deaminopenicillamine, 4-valine, 8-D-arginine] vasopressin.
  
  
  METHODS
  Human internal mammary artery segments (n = 218) were studied in organ baths. The inhibitory effects of the above vasodilators on AVP-mediated contraction were studied in two ways: relaxation with AVP precontraction and depression of the AVP-induced contraction after pretreatment with vasodilators.
  
  
  RESULTS
  All three calcium-channel antagonists caused limited relaxation (18.3%+/-5.4% for nifedipine, n = 11; 22.2%+/-3.8% for verapamil, n = 10; and 26.2%+/-7.5% for diltiazem, n = 9). The plasma concentration of calcium-channel antagonists had no significant depression effect on the AVP-induced contraction. In contrast, [1-deaminopenicillamine, 4-valine, 8-D-arginine] vasopressin caused full (100%, n = 11) and nitroglycerin caused nearly full (93%+/-3%, n = 10) relaxation. Pretreatment with [1-deaminopenicillamine, 4-valine, 8-D-arginine] vasopressin (10(-8), 10(-7), or 10(-6) mol/L, respectively) significantly increased the effective concentration for 50% of the AVP-induced contraction (10(-8.6)+/-10(0.1) mol/L, p = 0.009; 10(-7.8)+/-10(0.07) mol/L, p = 0.000; or 10(-6.9)+/-10(0.11) mol/L, p = 0.000 versus the control, 10(-9.24)+/-10(0.16) mol/L). However, nitroglycerin only slightly depressed the AVP-induced contraction.
  
  
  CONCLUSIONS
  [1-Deaminopenicillamine, 4-valine, 8-D-arginine] vasopressin may provide specific antispastic effect in either prophylaxis or treatment of the AVP-related vasospasm in the internal mammary artery. Nitroglycerin may be effective in treatment but has little effect on prophylaxis. Use of calcium-channel antagonists may have little benefit in AVP-related vasospasm.
authors.affiliation: Starr Academic Center, Providence Heart Institute, Department of Surgery, Oregon Health Sciences University, Portland, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: H Storm
authors.initials: HS
authors.lastname: Floten
authors.forename: Guo-Wei
authors.initials: GW
authors.lastname: He
mesh_terms: D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000502:physiology*; D001026:Coronary Artery Bypass; D023903:Coronary Restenosis / Q000503:physiopathology*; D046508:Culture Techniques; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects* / Q000503:physiopathology; D008875:Middle Aged; D009543:Nifedipine / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D001127:Arginine Vasopressin; C028799:argipressin, deaminopenicillamine(1)-Val(4)-; D014700:Verapamil; D004110:Diltiazem; D005996:Nitroglycerin; D009543:Nifedipine