Hemodynamic effects of endothelin-1 and big endothelin-1 in chronic hemodialysis patients

Increased plasma concentrations of endothelin-1 (ET-1) and big endothelin-1 (big ET-1) have been reported in patients with end-stage renal failure (ES RD). In the present study, which included hemodialysis (HD) patients with ( n = 21) and without (n = 32) ischemic heart disease, the putative associati on between plasma levels of ET-1 and big ET-1 and ischemic heart disease an d the influence of the dialysis procedure on ET concentrations was investig ated. This study also examined in an additional five HD patients without ca rdiac disease whether intravenously infused ET-1 and big ET-1 (0.2, 1, and 4 pmol/kg per min, each dose for 20 min) preserve their vasoactive potency and whether exogenous big ET-1, which in healthy humans is converted in the kidney, is still converted to ET-1 in ESRD. HD patients with ischemic hear t disease demonstrated higher plasma levels of ET-1 and big ET-1 than HD pa tients without this disorder, and HD reduced plasma ET-1 and big ET-1 conce ntrations. In HD patients, the big ET-1 infusion, resulting in a 1.5-fold i ncrease in plasma ET-1, caused a more marked and prolonged rise in mean art erial BP than ET-1 (20% versus 13%, P = 0.0001) and a slightly smaller but more prolonged decrease in estimated splanchnic blood flow than ET-1 (37% v ersus 44%, P = 0.02). Furthermore, big ET-1 lowered heart rate by 9% (P = 0 .01) but ET-1 did not. Plasma half-lives of ET-1 and big ET-1 were longer i n HD patients than in healthy humans. Thus, ET-1 and big ET-1 preserve thei r vasoactive potency, and circulating big ET-1 is still converted to active ET-1 in ESRD. Consequently, the increased plasma levels of ET-1 and big ET -1 noted in HD patients, especially in patients with ischemic heart disease , might play a role in the development of uremic cardiovascular complicatio ns.