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) E-1 in patients with intermittent claudication. Patients. material and 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 PGE(1) (60 mu g 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 PGE(1) 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.