RECIPROCAL INHIBITION OF NITRIC-OXIDE AND PROSTACYCLIN SYNTHESIS IN HUMAN SAPHENOUS-VEIN

1 Angiotensin II (AII) causes contraction of isolated rings of human s aphenous vein, responses that are attenuated by the presence of functi onal endothelium. In this study, we have investigated the mechanisms c ontrolling the release by AII of two endothelial-derived vasorelaxants , prostacyclin (PGI(2)) and nitric oxide (NO). 2 Myotropic and biochem ical changes were measured in response to AII. The biochemical respons es measured were the output of PGI(2) (as 6-oxo-PGF(1 alpha)) and of N O (as cyclic GMP). Inhibitors of cyclooxygenase (COX; piroxicam) or NO synthase (NOS; L-NAME), were added to the system to determine the inf luence of endogenous prostaglandins and NO on both myotropic and bioch emical responses. Furthermore, to mimic the effects of endogenous, PGI (2) or NO, exogenous forms of these relaxants were added, during inhib ition of their endogenous release. 3 Contractions of the rings of saph enous vein in response to AII (1-100 nM) were unaffected by treatment with either piroxicam (5 mu M) or L-NAME (200 mu M) individually. Howe ver, when these two inhibitors were used together, there was an increa se in the contractions in response to AII. 4 Biochemical analyses reve aled that during stimulation by AII, levels of PGI(2) and NO were enha nced when synthesis of the other vasodilator was inhibited, suggesting that endogenous NO inhibits PGI(2) synthesis and endogenous, PGI(2) o r another vasorelaxant PG can inhibit NO synthesis. 5 Exogenous PGI(2) (as iloprost) or NO (from glyceryl trinitrate) inhibited the increase d output of endogenous NO or PGI(2) respectively. 6 These results demo nstrate the presence, in human saphenous vein, of a mechanism which en sures that levels of vasodilatation are maintained through a compensat ory increase in one relaxant agonist when output of the other is decre ased. If present in vivo such a mechanism would be important in mainta ining saphenous vein graft patency as both PGI(2) and NO are not only vasodilators, but inhibit platelet aggregation and myoinitimal hyperpl asia, processes implicated in degeneration of graft function.