title: Unfractioned heparin produces vasodilatory action on human internal mammary artery by endothelium-dependent mechanisms.
abstract: The aim of this study was to investigate whether unfractioned heparin produces a direct vasodilatory effect on the human internal mammary artery (IMA) and the possible underlying mechanisms. Samples of redundant IMA were obtained from 20 patients undergoing coronary artery bypass graft surgery, and concentration-response curves to unfractioned heparin were constructed. Unfractioned heparin (0.5-6 U/mL) caused a concentration-dependent relaxation in the endothelium-intact human IMA rings precontracted with phenylephrine (10(-6) M). Removal of endothelium significantly inhibited the responses of human IMA to unfractioned heparin (P < 0.05). Nomega-Nitro-L-arginine methyl ester (L-NAME, 10(-4) M), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10(-5) M) and L-NAME (10(-4) M) plus ODQ (10(-5) M) partially reduced unfractioned heparin-induced vasodilatory response in endothelium-intact rings, whereas indomethacin alone had no effect. The vasodilatory effect of unfractioned heparin was completely inhibited by 40 mM KCl in the presence of L-NAME, ODQ, and indomethacin. These results clearly demonstrated that unfractioned heparin causes a concentration-dependent vasodilatation in human internal mammary artery, and this action seems to be via endothelium-dependent mechanisms, including generation of nitric oxide and endothelium-derived hyperpolarizing factor.
authors.affiliation: Department of Pharmacology, Akdeniz University Medical Faculty, Antalya, Turkey. ardatas@akdeniz.edu.tr
authors.forename: Arda
authors.initials: A
authors.lastname: Tasatargil
authors.forename: Ilhan
authors.initials: I
authors.lastname: Golbasi
authors.forename: Gulay
authors.initials: G
authors.lastname: Sadan
authors.forename: Edibe
authors.initials: E
authors.lastname: Karasu
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology*; D001685:Biological Factors / Q000502:physiology; D002315:Cardiopulmonary Bypass; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008323:Mammary Arteries / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D000925:Anticoagulants; D001685:Biological Factors; D004791:Enzyme Inhibitors; D011453:Prostaglandins; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D006493:Heparin; D019331:NG-Nitroarginine Methyl Ester