Effects of a 4-week treatment with prostaglandin E1 on plasma endothelin-1 release in patients with intermittent claudication.
OBJECTIVE
Endothelin-1 (ET-1) is a vasoconstrictor mitogenic peptide whose plasma concentrations are increased in patients with peripheral arterial occlusive disease (PAOD). The aim of this study was to investigate whether changes in plasma ET-1 concentrations occur after a 4-week treatment with prostaglandin (PG) E1 in patients with intermittent claudication.


METHODS
Twenty-four non-trained outpatients with Fontaine stage II PAOD (20 men and 4 women, mean age 63+/-7 years, age range 48-72 years) were randomized to receive over a 4-week period either PGE1 (60 microg given daily i.v. over 2 hours in 250 ml saline, n = 12) or placebo (250 ml saline, n = 12). Plasma levels of ET-1 were measured by radioimmunoassay at baseline and after treatment period. Before and after treatment pain-free walking distance (PFWD) and maximum walking distance (MWD) were evaluated by treadmill walking test as the target parameters for assessing treatment efficacy.


RESULTS
At week 4, PFWD and MWD significantly increased in comparison to baseline only in PGE1 treatment group (from 136+/-38 m to 246+/-95 m, p = 0.0004, and from 238+/-54 m to 411+/-137 m, p = 0.0001, respectively). At the end of the treatment period with PGE1, ET-1 plasma concentration decreased from 4.50+/-0.8 pmol/l to 3.6+/-1.1 pmol/l (p = 0.002), whereas it remained unchanged in placebo group. A significant correlation between the decrease in ET-1 plasma levels and the increase in the PFWD and MWD (r = -0.92, p < 0.0001; r = -0.78, p = 0.002, respectively) was detected in PGE1 treatment group.


CONCLUSIONS
Reduced ET-1 plasma concentrations after PGE1 treatment could be an index of improved endothelial function and/or could contribute to a reduction in vascular resistance and vessel wall growth in PAOD patients. Moreover, plasma ET-1 could be a marker of clinical improvement in these patients.
Mangiafico
R A
RA
Institute of Internal Medicine L. Condorelli, University of Catania, Italy.
Malatino
L S
LS
Santonocito
M
M
Messina
R
R
Attinà
T
T
Dell'Arte
S
S
Sarnataro
F
F
D000368:Aged; D000527:Alprostadil / Q000494:pharmacology / Q000627:therapeutic use*; D001157:Arterial Occlusive Diseases / Q000188:drug therapy / Q000503:physiopathology; D019332:Endothelin-1 / Q000097:blood*; D005080:Exercise Test; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007383:Intermittent Claudication / Q000188:drug therapy* / Q000503:physiopathology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011863:Radioimmunoassay; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*
D019332:Endothelin-1; D014665:Vasodilator Agents; D000527:Alprostadil