ENDOTHELIN AND CARDIOVASCULAR REMODELING IN END-STAGE RENAL-DISEASE

Background. Plasma endothelin (ET) is elevated in end-stage renal dise ase (ESRD), but the origin and consequences of this increase remain un clear. In the present study we analysed the relationships between plas ma ET levels and cardiovascular alterations in ESRD. Methods and resul ts. Common carotid artery (CCA) intima-media thickness (IMT) and diame ter, atherosclerotic plaque occurrence, and left ventricular (LV) geom etry and function were determined by ultrasound imaging in 76 haemodia lysis patients and in 57 age-, sex-, and blood pressure-matched contro ls. Arterial stiffness was evaluated via carotid-femoral pulse wave ve locity (CF-PWV), forearm post-ischaemic vasodilation was measured by v enous plethysmography, and plasma ET levels were determined using a sp ecific immunoenzymoassay. Compared with controls, ESRD patients had el evated plasma ET levels (1.6 +/- 1.4 vs 4.6 +/- 3.8 pg/ml; P < 0.001), increased LV mass (P < 0.001), increased CCA-IMT (P < 0.001), a highe r prevalence of atherosclerotic plaques (P < 0.001) and increased CF-P WV (P < 0.01). Plasma ET levels correlated positively with LV outflow velocity integral(r = 0.57; P < 0.0001), stroke index (P < 0.01), and baseline forearm blood flow (P < 0.001) which were all significantly h igher in ESRD patients than in controls (P < 0.01). After adjustment f or age, blood pressure, haemoglobin levels, gender and body dimensions , plasma ET levels were significantly correlated to LV mass (r = 0.46; P < 0.001), CCA-IMT and CCA intima -media cross-sectional area (r = 0 .41; P < 0.001), and CF-PWV (P < 0.05). Post-ischaemic forearm vasodil ation was decreased in ESRD (85 +/- 31 vs 119 +/- 28%; P < 0.001) and there was a negative correlation between post-ichaemic flow recovery a nd ET levels (r = -0.49; P < 0.001). In ESRD patients, plasma ET level s were positively and independently correlated with the prevalence of CCA atherosclerotic plaque (P < 0.01). Conclusions. These results indi cate that the increased plasma ET levels in ESRD patients are associat ed with left ventricular hypertrophy and arterial intima-media thicken ing, suggesting that increased ET concentrations in ESRD patients may be of pathophysiological significance in the process of cardiovascular remodelling.