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 potential participant in the pathophysiological processes of the development of atherosclerotic lesions and disease states associated with vasoconstriction and vasospasm.
Methods: To investigate the endothelin-1 release in response to dynamic exercise 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 disease 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 vein, at the onset of claudication pain, and 10 minutes after exercise.
Results: Mean plasma endothelin-concentrations during the stress test increased significantly in the patients with arterial disease, rising from basal values of 4.4 +/- 0.6 pmol/L to values of 8.9 +/- 0.7 pmol/L at the end of the test (p < 0.0001), whereas it did not change significantly in control subjects (rising from 2.6 +/- 0.4 pmol/L to 2.7 +/- 0.5 pmol/L). Further, plasma endothelin- in the patients with arterial disease was at all times higher than in the control subjects (p < 0.0001).
Conclusions: In conclusion, this study shows that in patients with peripheral arterial occlusive disease, plasma endothelin-1 increases after treadmill exercise performed until claudication pain supervenes. Raised endothelin-1 could be a marker of ischaemic acute endothelial damage and/or could contribute to increase the vascular resistance in ischaemic limbs of these patients during dynamic exercise by promoting arterial/arteriolar vasoconstriction or vasospasm.