title: The interaction between human urotensin II and vasodilator agents in human internal mammary artery with possible clinical implications.
abstract: BACKGROUND
  Graft spasm in the internal mammary artery (IMA) may occur after coronary artery bypass grafting (CABG). We investigated the effect of human urotensin II (hU-II), a cyclic peptide hormone present in human blood and tissues, and the effect of vasodilators on hU-II-mediated response in human IMA.
  
  
  METHODS
  Fresh IMA segments (n=114) taken from 50 patients undergoing CABG were studied in a myograph. The interaction between hU-II and various calcium antagonists or glyceryl trinitrate (GTN) was investigated in 2 ways: relaxing effect of vasodilators on the hU-II-induced precontraction and depressing effect of vasodilator agents on the contraction caused by hU-II (n=6 to 10 in each subgroup).
  
  
  RESULTS
  Human urotensin II caused contractile response in all human IMA. In potassium chloride-contraction, full (nifedipine: 99.1 %±2.7%) or nearly full (diltiazem: 93.5%±4.8%) relaxation with 30.9-fold higher potency to nifedipine than to diltiazem (EC50 [effective concentration causing 50% of maximal response] -8.24±0.21 vs -6.75±0.20 log M, p=0.0002) and in hU-II-contraction, nearly full relaxation (nifedipine: 90.6%±4.6%; diltiazem: 95.0%±1.7%) with 5.8-fold higher potency to nifedipine than to diltiazem (EC50 -7.55±0.26 vs -6.79±0.25 log M, p=0.03) were observed. The GTN caused nearly full relaxation (93.1%±4.8%) but GTN pretreatment had limited effect in prevention of the hU-II-induced contraction, whereas diltiazem and nifedipine reduced subsequent contraction to hU-II.
  
  
  CONCLUSIONS
  Human urotensin II is a potent vasoconstrictor in human IMA. Calcium antagonists and GTN relax the contraction caused by hU-II with different potencies. However, calcium antagonists are more effective than GTN in preventing the contraction induced by hU-II. These findings may have clinical implications in CABG.
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: 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: D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003329:Coronary Vasospasm / Q000503:physiopathology*; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D008323:Mammary Arteries / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009204:Myocardial Revascularization; D009543:Nifedipine / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D011183:Postoperative Complications / Q000503:physiopathology*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors; D014579:Urotensins / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D010446:Peptide Fragments; D043562:Receptors, G-Protein-Coupled; C121697:UTS2R protein, human; D014579:Urotensins; D014665:Vasodilator Agents; C492079:urotensin II (4-11), Pen(5)-Trp(7)-Orn(8)-; C029677:urotensin II; D004110:Diltiazem; D005996:Nitroglycerin; D009543:Nifedipine