The vascular endothelin system is not overactive in normotensive hemodialysis patients.

Abstract

The hemodynamic significance of elevated endothelin-1 (ET) plasma levels in hemodialysis (HD) patients is unknown. Therefore, we studied the role of ET in the regulation of vascular tone in normotensive HD patients and matched healthy controls (C). The forearm blood flow (FBF) responses to adenosine, norepinephrine, the ET-A receptor antagonist BQ-123 (40 nmol/min), the ET-B receptor antagonist BQ-788 (1 and 50 nmol/min), and ET (5 pmol/min) were measured. Results are percent of baseline change +/- SEM (baseline = 100%). Responses to adenosine and norepinephrine were both unchanged in HD. In HD, BQ-123 increased FBF less than in C (133 +/- 9 vs. 178 +/- 27%; P = 0.02). BQ-788 failed to change FBF in C but decreased FBF to 83 +/- 4% in HD. Compared to BQ-123 alone, BQ-123 plus BQ-788 (50 nmol/min) caused an additional increase of FBF (234 +/- 32%, P < 0.001) in C, but not in HD (139 +/- 14%). This additional increase was absent when BQ-788 was co-infused at 1 nmol/min. ET reduced FBF comparably in both groups. Resistance vessels of HD patients have unremarkable contractile properties, as shown by responses to adenosine and norepinephrine. In HD, the basal vascular ET-mediated tone is reduced. The main action of the ET-B receptor in C is vasoconstrictive, which also is blunted in HD. The intact response to exogenous ET indicates the normal function of ET receptors in HD. Our results could be explained by a reduced generation or reduced metabolic clearance rate of ET in normotensive HD patients. Controversy remains concerning the role of the ET-B receptor when comparing the present data with previously published literature.