British Journal of Anaesthesia, Vol 76, Issue 1 122-129, Copyright © 1996 by The Board of Management and Trustees of the British Journal of Anaesthesia
M. B. Vroom, M. Pfaffendorf, H. B. van Wezel and P. A. van Zwieten
In the present study, we investigated if the relaxant effects of
phosphodiesterase (PDE) III inhibitors on human vessels could be inhibited
by a nitric oxide synthase blocker, L-NAME, or by a blocker of
ATP-sensitive potassium channels (KATP), glibenclamide. The experiments
were performed using an isometric myograph in isolated human s.c. small
arteries obtained from healthy donors. After a priming procedure consisting
of exposure to high potassium (120 mmol litre-1) solutions, phenylephrine
10 mumol litre-1 and an equilibrium period of 30 min, the preparations were
contracted with a thromboxane A2 mimetic agent, U46619 1 mumol litre-1.
Subsequently, cumulative concentration- response curves were constructed
for the selective PDE III inhibitors amrinone, milrinone and enoximone, and
for theophylline and dipyridamole, with and without the addition of L-NAME
100 mumol litre-1 or glibenclamide 1 mumol litre-1. Addition of L-NAME to
the organ bath resulted in significantly higher pEC50 values (-log of the
concentration required 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 amrinone,
enoximone, theophylline and dipyridamole are not dependent on nitric oxide
release or on interaction with KATP channels. However, the effect of
milrinone may be partly endothelium-dependent in human vessels in vitro.
LABORATORY INVESTIGATIONS
Effect of phosphodiesterase inhibitors on human arteries in vitro
Department of Anaesthesiology, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands; Department of Pharmacotherapy and Cardiology, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands
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