title: Dipeptidyl peptidase 4 inhibitor reduces intimal hyperplasia in rabbit autologous jugular vein graft under poor distal runoff.
abstract: Dipeptidyl peptidase 4 inhibitors are widely used in patients with type 2 diabetes mellitus to accomplish glycemic control through an increase in the blood glucagon-like peptide 1 (GLP-1) concentration. These agents also inhibit vascular inflammation (eg, in atherosclerosis). This study was undertaken to determine whether and how vildagliptin (a potent dipeptidyl peptidase 4 inhibitor) might reduce intimal hyperplasia in vein grafts.
  
  
  
  Twelve rabbits were randomly divided into two groups; one group received vildagliptin orally (10 mg/kg/d; n = 6), whereas the control group (n = 6) did not. Vildagliptin administration was started 7 days before rabbits underwent interposition reversed autologous jugular vein grafting and ended at graft harvesting (28 days after the operation). Histochemical changes in the vascular wall were examined, as were changes in the acetylcholine-induced effects on the endothelial Ca(2+) concentration ([Ca(2+)]i) and endothelium-dependent relaxation.
  
  
  
  Under fasting conditions, vildagliptin increased the plasma GLP-1 concentration, without affecting plasma glucose or insulin. Acetylcholine induced endothelium-dependent relaxation only in the vildagliptin group, and this was blocked by the nitric oxide synthase inhibitor N(ω)-nitro-l-arginine. Acetylcholine did not modify the endothelial [Ca(2+)]i in either the control or vildagliptin group. Intimal hyperplasia was significantly less in the vildagliptin group (0.11 ± 0.02 mm, n = 5) than in the controls (0.31 ± 0.06 mm, n = 4; P < .01).
  
  
  
  Vildagliptin increased the plasma GLP-1 concentration. It also enhanced acetylcholine-induced [Ca(2+)]i-independent endothelial nitric oxide release and reduced vein graft intimal hyperplasia, independently of any glycemic control action.
authors: Department of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Nagoya City, Japan; Division of Vascular Surgery, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya City, Japan.
authors: Akio
authors: A
authors: Koyama
authors: Division of Vascular Surgery, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya City, Japan.
authors: Kimihiro
authors: K
authors: Komori
authors: Department of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Nagoya City, Japan.
authors: Ryo
authors: R
authors: Otsuka
authors: Department of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Nagoya City, Japan.
authors: Junko
authors: J
authors: Kajikuri
authors: Department of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Nagoya City, Japan. Electronic address: titoh@med.nagoya-cu.ac.jp.
authors: Takeo
authors: T
authors: Itoh
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D064592:Autografts; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D006965:Hyperplasia; D007601:Jugular Veins / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology / Q000637:transplantation*; D008297:Male; D058426:Neointima; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009570:Nitriles / Q000008:administration & dosage / Q000494:pharmacology*; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D000077597:Vildagliptin
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D009570:Nitriles; D011759:Pyrrolidines; D014665:Vasodilator Agents; D009569:Nitric Oxide; D052216:Glucagon-Like Peptide 1; D019001:Nitric Oxide Synthase; D018819:Dipeptidyl Peptidase 4; D000077597:Vildagliptin; D000218:Adamantane; D002118:Calcium