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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.

Background: Endothelin-1 (ET-1), a vasoconstrictor and mitogenic endothelium-derived peptide, has been considered as a marker for endothelial damage and potential contributor to the development of the atherogenic process., Methods: To evaluate the pattern of plasma ET-1 secretion in non-insulin-dependent diabetes mellitus (NIDDM) and nondiabetic patients with chronic arterial obstructive disease (CAOD) of the lower limbs, plasma levels of ET-1 were determined in 12 NIDDM patients (10 men and 2 women; mean age 63+/-8 years) with CAOD of the lower limbs at Fontaine stage II and in 12 nondiabetic patients (11 men and 1 woman; mean age 62+/-4 years) with comparable arteriopathy. Ten normal subjects comprised the control population., Results: The plasma levels of ET-1 in NIDDM patients with CAOD of the lower limbs were 5.7+/-0.3 pmol/L, which represented a significant (p<0.001) difference from the values in nondiabetic patients with comparable arteriopathy (4.1+/-0.6 pmol/L) and those in the control group (2.7+/-0.7 pmol/L). Plasma levels of ET-1 showed a significant (p<0.0001) positive correlation with the levels of fasting insulin in NIDDM patients with CAOD of the lower limbs. Increased plasma ET-1 could reflect a major and/or more diffuse endothelial cell damage or dysfunction in NIDDM than in nondiabetic patients with comparable CAOD of the lower limbs. Augmented mitogenic ET-1 levels could also have a role both in diabetic and nondiabetic angiopathy., Conclusions: The positive correlation between ET-1 plasma levels and fasting insulin levels in NIDDM patients with CAOD of the lower limbs suggests that the increased ET-1 release could be related to the augmented insulin secretion in these patients. Insulin-related overproduction of ET-1 could promote the atherogenic process and enhance the vascular tone to a greater extent in NIDDM than in nondiabetic patients with CAOD of the lower limbs.

The present study was designed to investigate the pattern of circulating endothelin-1 (ET-1), a potent vasoconstricting mitogenic endothelium-derived peptide, in relation to primary increase in serum cholesterol in humans. We measured plasma ET-1 concentrations by radioimmunoassay (Amersham, UK) in 8 patients (6 females and 2 males, aged 42-62 years) with primary hypercholesterolemia, non-smokers, without evidence of cardiovascular disease, and in 8 healthy sex-and age-matched control subjects. The mean (+/- SD) values of serum total cholesterol, low-density-lipoprotein (LDL) cholesterol, high-density-lipoprotein (HDL) cholesterol and triglycerides in the hypercholesterolemic subjects were 7.2 +/- 1.1 mmol/L, 5.1 +/- 1.1 mmol/L, 1.0 +/- 0.1 mmol/L and 2.4 +/- 0.9 mmol/L, respectively. The lipid profile of the controls showed a total cholesterol of 4.6 +/- 0.3 mmol/L, LDL cholesterol of 3.0 +/- 0.2 mmol/L, HDL cholesterol of 1.0 +/- 0.1 mmol/L and triglycerides of 1.2 +/- 0.2 mmol/L. The mean ET-1 plasma levels in the hypercholesterolemic patients were significantly higher than in the controls (4.2 +/- 0.1 pmol/L and 2.2 +/- 0.7 pmol/L, respectively, p < 0.001). Our data of raised circulating ET-1 in hypercholesterolemic patients without evidence of atherosclerosis suggest that an exaggerated release of ET-1 could contribute: 1) to impair endothelium-dependent vasodilation; 2) to promote the atherogenic process in hypercholesterolemia. Finally, it could represent a marker for hypercholesterolemic endothelial damage.

To investigate the effects of postural changes and upright exercise on atrial natriuretic peptide release and renin-angiotensin-aldosterone system behavior in patients with venous valvular insufficiency, plasma ANP, plasma renin activity and aldosterone were measured in 11 patients with venous disease and in 11 age-matched controls. In patients with large varicose veins and venous valvular dysfunction, standing was associated with a greater fall in circulating ANP levels (p < 0.05) and upright exercise was accompanied by a smaller rise in ANP concentrations (p < 0.05) as compared with controls. A significant (p < 0.001) inverse relationship was found between the number of venous segments with reflux and both upright and exercise plasma ANP concentrations (r = -0.91; r = -0.84, respectively). In the two groups the response of the renin-angiotensin-aldosterone system to upright position and physical stress was similar. These results suggest that a decreased atrial stretch, due to a reduced venous return, could account for the blunted ANP response to erect posture and exercise in patients with venous valvular incompetency.