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. 1996 Jun;118(3):643–648. doi: 10.1111/j.1476-5381.1996.tb15449.x

Reciprocal inhibition of nitric oxide and prostacyclin synthesis in human saphenous vein.

J E Barker 1, Y S Bakhle 1, J Anderson 1, T Treasure 1, P J Piper 1
PMCID: PMC1909713  PMID: 8762089

Abstract

1. 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). 2. Myotropic and biochemical changes were measured in response to AII. The biochemical responses measured were the output of PGI2 (as 6-oxo-PGF1 alpha) 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. 3. Contractions of the rings of saphenous vein in response to AII (1-100 nM) were unaffected by treatment with either piroxicam (5 microM) or L-NAME (200 microM) individually. However, when these two inhibitors were used together, there was an increase in the contractions in response to AII. 4. 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. 5. Exogenous PGI2 (as iloprost) or NO (from glyceryl trinitrate) inhibited the increased output of endogenous NO or PGI2 respectively. 6. 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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Selected References

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