EFFECT OF PHOSPHODIESTERASE INHIBITORS ON HUMAN ARTERIES IN-VITRO

In the present study, we investigated if the relaxant effects of phosp hodiesterase (PDE) III inhibitors on human vessels could be inhibited by a nitric oxide synthase blocker. L-NAME, or by a blocker of ATP-sen sitive potassium channels (K-ATP), glibenclamide. The experiments were performed using an isometric myograph in isolated human s.c. small ar teries obtained from healthy donors. After a priming procedure consist ing of exposure to high potassium (120 mmol litre(-1)) solutions, phen ylephrine 10 mu mol litre(-1) and an equilibrium period of 30 min, the preparations were contracted with a thromboxane A(2) mimetic agent, U 46619 1 mu mol litre(-1). Subsequently, cumulative concentration-respo nse curves were constructed for the selective PDE III inhibitors amrin one, milrinone and enoximone, and for theophylline and dipyridamole, w ith and without the addition of L-NAME 100 mu mol litre(-1) or glibenc lamide 1 mu mol litre(-1). Addition of L-NAME to the organ bath result ed in significantly higher pEC(50) values (-log of the concentration r equired for 50% relaxation) for milrinone compared with the control: 2 .77 (SEM 0.24) mol litre(-1) (n = 5) vs 3.49 (0.17) mol litre(-1) (n = 7) (P < 0.05). There was no significant difference between any other group. From our data we conclude that the relaxant properties of amrin one, enoximone, theophylline and dipyridamole are not dependent on nit ric oxide release or on interaction with K-ATP channels. However, the effect of milrinone may be partly endothelium-dependent in human vesse ls in vitro.