The effects of iloprost infusion on microcirculation is independent of nitric oxide metabolites and endothelin-1 in chronic peripheral ischaemia.
BACKGROUND
Endothelial vascular tone modulators are thought to be involved in aetiopathogenesis of systemic sclerosis (SS) and of peripheral artery occlusive disease (PAOD). Iloprost, a prostacyclin (PGI2) analogue, induces clinical benefit in patients suffering from peripheral ischaemia. This study was performed to investigate the effect of this drug on endothelial function in vivo to elucidate the role of vascular tone modulators.


METHODS
Fourteen PAOD and 15 SS patients were treated for 24 and 10 days respectively. On the first day, before and after therapy, nitric oxide metabolites (NO2-/NO3-) and endothelin-1 (ET-1) plasma concentrations were detected; moreover, the endothelium-dependent vasodilatation in response to artificial ischaemia was evaluated by means of an echo-Doppler device.


RESULTS
The echo-Doppler evaluation showed that the percentage of arterial reactive dilatation was not modified by placebo or by iloprost, and that the increase in blood velocity flow lasted for a significant longer time after drug infusion (226.79 +/- 17.49 vs. 310.71 +/- 36.32 s; P > 0.04). NO2-/NO3- and ET-1 plasma concentration were higher in patients than in control subjects (P < 0.004). After 6 h of iloprost infusion, no significant modifications were detected.


CONCLUSIONS
This study provides evidence that iloprost enhances the microvascular functional capacity and clinical benefit for patients. The effects of the drug seem to be independently or not directly correlated with its interactions with vascular tone modulators such as NO2-/NO3- or ET-1.
Mazzone
A
A
Department of Internal Medicine and Nephrology, University of Pavia, IRCCS S. Matteo Hospital, Italy.
Cusa
C
C
Bucci
L
L
Vezzoli
M
M
Ghio
S
S
Buggia
I
I
Regazzi
M B
MB
Fossati
G
G
Mazzucchelli
I
I
Gritti
D
D
D000328:Adult; D000368:Aged; D001157:Arterial Occlusive Diseases / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D002908:Chronic Disease; D019332:Endothelin-1 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D006801:Humans; D016285:Iloprost / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007511:Ischemia / Q000188:drug therapy; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D012595:Scleroderma, Systemic / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D014463:Ultrasonography; D014665:Vasodilator Agents / Q000627:therapeutic use*
D019332:Endothelin-1; D009566:Nitrates; D009573:Nitrites; D014665:Vasodilator Agents; D009569:Nitric Oxide; D016285:Iloprost