Effects of a 4-week treatment with prostaglandin E1 on plasma endothelin-1 release in patients with intermittent claudication
Mangiafico, R.A.; Malatino, L.S.; Santonocito, M.; Messina, R.; Attinà, T.; Dell'Arte, S.; Sarnataro, F.
International Journal of Clinical Pharmacology and Therapeutics 37(7): 347-351
1999
ISSN/ISBN: 0946-1965 PMID: 10442509 Document Number: 511703
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. Patients, material and methods: Twenty-four non-trained out-patients 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 mug 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 week4, 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.