The evaluation of the no-independent vasodilatative effect of iloprost in isolated perfused Guinea pig hind limbs.
OBJECTIVE
In critical limb ischemia vasodilatators play an important role in the treatment of the disease. Considering that the endothelium is seriously damaged in these patients, we wanted to evaluate if the vasodilatative effect of iloprost does or does not depend on the endothelium by using the model of the isolated perfused guinea pig hind limb.


METHODS
A catheter was inserted via the distal aorta and common iliac artery. After stabilization, iloprost was administered at a dosage of 0.1 microM. In a subsequent series of experiments precontraction of the peripheral vascular bed was achieved with 40 mM KCl followed by 0.1 microM iloprost. In a 3rd series of experiments L-NAME (100 microM) was administered after the equilibration period for 30 minutes, followed by 0.1 microM iloprost. In the 4th series of experiments, after the administration of L-NAME (100 microM), KCl (40 mM) was administered to precontract the vascular bed and iloprost 0.1 microM was added.


RESULTS
The administration of iloprost alone and after addition of KCL induced a significant decrease in vascular resistance(-49.6+/-14.1% [x+/-SEM, n=7]). The addition of L-NAME did not affect vascular resistance. The consecutive addition of iloprost reduced vascular resistance significantly (-4.2+/-0.7% [x+/-SEM, n=7]). After addition of L-NAME 100 microM and precontraction with KCl 40 mM, iloprost once again significantly reduced peripheral vascular resistance (-51.5+/-14.4% [x+/-SEM, n=6]). Reduction of peripheral vascular resistance by iloprost was comparable to that without L-NAME.


CONCLUSIONS
Our data show that iloprost at a dosage of 0.1 microM achieves a significant reduction in peripheral vascular resistance and that the vasodilatative effect of iloprost is independent of NO. Iloprost therefore seems to be an ideal vasodilatative drug for the treatment of patients with impaired endothelial function.
Brodmann
M
M
Division of Pharmacotherapy, Department of Internal Medicine, Karl-Franzens University, Graz, Austria. marianne.brodmann@kfunigraz.ac.at
Lischnig
U
U
Lang
B
B
Lueger
A
A
Pilger
E
E
Stark
G
G
D000818:Animals; D005260:Female; D006168:Guinea Pigs; D006614:Hindlimb / Q000098:blood supply* / Q000187:drug effects*; D016285:Iloprost / Q000494:pharmacology*; D008297:Male; D010477:Perfusion; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D016285:Iloprost