Treadmill exercise-induced release of endothelin-1 in patients with peripheral arterial occlusive disease at Fontaine stage IIb

Background Endothelin-1 (ET-1) is an endothelial vasoconstrictor mitogenic peptide which is thought to be a marker of endothelial damage and a potenti al participant in the pathophysiological processes of the development of at herosclerotic lesions and disease states associated with vasoconstriction a nd vasospasm. Methods. To investigate the endothelin-1 release in response to dynamic exe rcise in patients with peripheral arterial occlusive disease (PAOD), plasma concentrations were determined by radioimmunoassay in 16 patients (14 men, 2 women, mean age 56.2+/-8.1 years) with peripheral arterial occlusive dis ease at Fontaine stage IIb and in 10 control subjects (8 men, 2 women, mean age 58.1+/-7.2 years) in normal health during treadmill testing (slope 5%, speed 3 km/hr). Blood samples were collected at rest from an antecubital v ein, at the onset of claudication pain, and 10 minutes after exercise. Results. Mean plasma endothelin-1 concentrations during the stress test inc reased significantly in the patients with arterial disease, rising from bas al values of 4.4+/-0.6 pmol/L to values of 8.9+/-0.7 pmol/L at the end of t he test (p<0.0001), whereas it did not change significantly in control subj ects (rising from 2.6+/-0.4 pmol/L to 2.7+/-0.5 pmol/L). Further, plasma en dothelin-1 in the patients with arterial disease was at all times higher th an in the control subjects (p<0.0001). Conclusions. In conclusion, this study shows that in patients with peripher al arterial occlusive disease, plasma endothelin-1 increases after treadmil l exercise performed until claudication pain supervenes. Raised endothelin- 1 could be a marker of ischaemic acute endothelial damage and/or could cont ribute to increase the vascular resistance in ischaemic limbs of these pati ents during dynamic exercise by promoting arteria/arteriolar vasoconstricti on or vasospasm.