Abstract
Background
The vasoactive effect of nicorandil on coronary arteries is well known. Nicorandil
exerts its vasodilatory effect through a dual mechanism of action: involving on the
one hand cyclic guanosine monophosphate (c GMP) as a nitrovasodilatator, and on the
other hand, acting as a potassium channel opener.
Objective
To address the question if nicorandil works in peripheral arteries, its effect on
peripheral vascular resistance was evaluated in isolated perfused guinea pig hind
limbs.
Methods
A catheter was inserted via the distal aorta and common iliac artery. Perfusion pressure
was monitored under constant perfusion with Tyrode's solution, therefore changes in
perfusion pressure represent changes in vascular resistance. After stabilization precontraction
of the peripheral vascular bed was achieved with noradrenaline 3 μM and nicorandil
was added in concentrations of 1, 10 and 100 μM.
The effect of nicorandil (1, 10 and 100 μM) was tested in the presence of l-NAME and glybenclamide.
Results
A significant reduction of vascular peripheral resistance was already achieved at
a concentration of 1 μM nicorandil (30.3±6.1%, mean S.E.M., p<0.001). At a concentration of 100 μM nicorandil the reduction of peripheral vascular
resistance was 94.4±16.4%.
Peripheral vascular resistance was less but nearly comparable reduced by nicorandil
(100 μM) if the endothelial NO effect was inhibited by l-NAME (58.6±18.6%) or if the ATP-dependent potassium channels were blocked by glybenclamide (56.4±14.6%).
Conclusions
In peripheral arteries the nitrovasodilator effect of nicorandil is nearly comparable
to the potassium agonistic effect, and the concentration, which is necessary to reduce
peripheral vascular resistance significantly, is comparable with dosages necessary
for reduction of coronary resistance.
Keywords
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Article info
Publication history
Published online: August 01, 2005
Accepted:
June 26,
2005
Received in revised form:
June 24,
2005
Received:
April 17,
2005
Identification
Copyright
© 2005 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
