NITRIC-OXIDE SYNTHASE AND ADENYLYL AND GUANYLYL CYCLASE ACTIVITY IN PORCINE INTERPOSITION VEIN GRAFTS

Background. A high proportion of autologous saphenous vein grafts occl ude as the result of intimal thickening. Blood vessels synthesize subs tances that may inhibit such intimal thickening. These include cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGM P), which are stimulated by prostacyclin and nitric oxide, respectivel y. The prostacyclin-cAMP and nitric oxide-cGMP axes were therefore inv estigated in porcine vein grafts. Methods. Saphenous vein-carotid arte ry interposition graft procedures were carried out in pigs. One month after the operation, ungrafted saphenous veins, vein grafts, and carot id arteries were excised, the formation of cAMP and cGMP was assessed by radioimmunoassay, and the nitric oxide synthase content was determi ned by autoradiography. Results. The formation of cAMP and nitroprussi de-stimulated cGMP was significantly diminished in vein grafts compare d with ungrafted saphenous veins and carotid arteries. Calimycin-stimu lated cGMP synthesis (nitric oxide release dependent) and the endothel ial nitric oxide synthase content (autoradiography) were significantly elevated in vein grafts compared with ungrafted saphenous veins but w ere significantly less than those in carotid arteries. Conclusions. Ad enylyl and guanylyl cyclase activity are down-regulated in vein grafts , which may contribute to the development of intimal and medial thicke ning. Nitric oxide release and endothelial nitric oxide synthase conte nt are up-regulated in vein grafts, which is indicative of an adaptati on to the arterial conditions of shear stress and pulsatile pressure. (C) 1997 by The Society of Thoracic Surgeons.