title: Nitric oxide synthase and adenylyl and guanylyl cyclase activity in porcine interposition vein grafts.
abstract: BACKGROUND
  A high proportion of autologous saphenous vein grafts occlude as the result of intimal thickening. Blood vessels synthesize substances that may inhibit such intimal thickening. These include cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which are stimulated by prostacyclin and nitric oxide, respectively. The prostacyclin-cAMP and nitric oxide-cGMP axes were therefore investigated in porcine vein grafts.
  
  
  METHODS
  Saphenous vein-carotid artery interposition graft procedures were carried out in pigs. One month after the operation, ungrafted saphenous veins, vein grafts, and carotid arteries were excised, the formation of cAMP and cGMP was assessed by radioimmunoassay, and the nitric oxide synthase content was determined by autoradiography.
  
  
  RESULTS
  The formation of cAMP and nitroprusside-stimulated cGMP was significantly diminished in vein grafts compared with ungrafted saphenous veins and carotid arteries. Calimycin-stimulated cGMP synthesis (nitric oxide release dependent) and the endothelial nitric oxide synthase content (autoradiography) were significantly elevated in vein grafts compared with ungrafted saphenous veins but were significantly less than those in carotid arteries.
  
  
  CONCLUSIONS
  Adenylyl and guanylyl cyclase activity are down-regulated in vein grafts, which may contribute to the development of intimal and medial thickening. Nitric oxide release and endothelial nitric oxide synthase content are up-regulated in vein grafts, which is indicative of an adaptation to the arterial conditions of shear stress and pulsatile pressure.
authors.affiliation: Bristol Heart Institute, University of Bristol, United Kingdom.
authors.forename: J Y
authors.initials: JY
authors.lastname: Jeremy
authors.forename: M R
authors.initials: MR
authors.lastname: Dashwood
authors.forename: M
authors.initials: M
authors.lastname: Timm
authors.forename: M B
authors.initials: MB
authors.lastname: Izzat
authors.forename: D
authors.initials: D
authors.lastname: Mehta
authors.forename: A J
authors.initials: AJ
authors.lastname: Bryan
authors.forename: G D
authors.initials: GD
authors.lastname: Angelini
mesh_terms: D000222:Adaptation, Physiological; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D006162:Guanylate Cyclase / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000032:analysis*; D011863:Radioimmunoassay; D012501:Saphenous Vein / Q000637:transplantation*; D013552:Swine; D015854:Up-Regulation / Q000502:physiology
chemical_list: D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D006152:Cyclic GMP