Angiotensin II (AII) causes contraction of isolated rings of human saphenous vein, responses that are attenuated by the presence of functional endothelium. In this study, we have investigated the mechanisms controlling the release by AII of two endothelial‐derived vasorelaxants, prostacyclin (PGI2) and nitric oxide (NO). Myotropic and biochemical changes were measured in response to AII. The biochemical responses measured were the output of PGI2 (as 6‐oxo‐PGF1α) and of NO (as cyclic GMP). Inhibitors of cyclo‐oxygenase (COX; piroxicam) or NO synthase (NOS; L‐NAME), were added to the system to determine the influence of endogenous prostaglandins and NO on both myotropic and biochemical responses. Furthermore, to mimic the effects of endogenous, PGI2 or NO, exogenous forms of these relaxants were added, during inhibition of their endogenous release. Contractions of the rings of saphenous vein in response to AII (1–100 nM) were unaffected by treatment with either piroxicam (5 μm) or L‐NAME (200 μm) individually. However, when these two inhibitors were used together, there was an increase in the contractions in response to AII. Biochemical analyses revealed that during stimulation by AII, levels of PGI2 and NO were enhanced when synthesis of the other vasodilator was inhibited, suggesting that endogenous NO inhibits PGI2 synthesis and endogenous, PGI2 or another vasorelaxant PG can inhibit NO synthesis. Exogenous PGI2 (as iloprost) or NO (from glyceryl trinitrate) inhibited the increased output of endogenous NO or PGI2 respectively. These results demonstrate the presence, in human saphenous vein, of a mechanism which ensures that levels of vasodilatation are maintained through a compensatory increase in one relaxant agonist when output of the other is decreased. If present in vivo such a mechanism would be important in maintaining saphenous vein graft patency as both PGI2 and NO are not only vasodilators, but inhibit platelet aggregation and myoinitimal hyperplasia, processes implicated in degeneration of graft function.

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1. The saphenous vein (SV) and internal thoracic artery (ITA) are the most commonly used conduits for coronary artery bypass surgery (CABS). The ITA shows better long term patency than the SV, at least in part due to their different responses to agonists, as well as physical differences between the ITA and SV at the time of grafting. 2. Angiotensin II (A II), a potent endogenous vasoconstrictor circulates at augmented levels during and after CABS, but little is known about the effects of A II on the SV and ITA. 3. We studied the contractile effects of A II on SV and ITA as intact rings from a heterogeneous group of patients undergoing CABS. Two groups of SV samples were studied; freshly excised SV (FSV) with no further manipulation and SV that had been surgically prepared for use as a bypass conduit (PSV). We also assessed the function of the endothelium in FSV, PSV and ITA, by measuring the relaxation of preconstricted rings to bradykinin. In some tissues endothelial presence was examined histologically. 4. Surgical preparation of SV affected the contractile ability of the smooth muscle, as PSV contracted less than FSV to potassium chloride (KCl, 90 mM) (P < 0.0001). Loss of endothelial function was seen in 25% of FSV, 50% of PSV and 33% of ITA. 5. A II caused concentration dependent contractions in all rings, over the same concentration range (1 nM‐100 nM). In rings of FSV the presence of functional endothelium attenuated the response, median values with endothelium being less than half that without endothelium (P < 0.0007, at 100 nM).(ABSTRACT TRUNCATED AT 250 WORDS)

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