The effect of the K+ agonist nicorandil on peripheral vascular resistance.
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 microM and nicorandil was added in concentrations of 1, 10 and 100 microM. The effect of nicorandil (1, 10 and 100 microM) 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 microM nicorandil (30.3+/-6.1%, mean S.E.M., p < 0.001). At a concentration of 100 microM nicorandil the reduction of peripheral vascular resistance was 94.4+/-16.4%. Peripheral vascular resistance was less but nearly comparable reduced by nicorandil (100 microM) 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.
Brodmann
Marianne
M
Working group of Clinical Pharmacotherapy, Department of Internal Medicine, Medizinische Universität Graz, Austria. marianne.brodmann@meduni-graz.at
Lischnig
Ulrike
U
Lueger
Andreas
A
Stark
Gerhard
G
Pilger
Ernst
E
D000818:Animals; D005260:Female; D006168:Guinea Pigs; D008297:Male; D020108:Nicorandil / Q000494:pharmacology*; D015221:Potassium Channels / Q000819:agonists*; D014655:Vascular Resistance / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D015221:Potassium Channels; D014665:Vasodilator Agents; D020108:Nicorandil