Endothelin ETA receptor-subtype specific antagonism does not mitigate the acute systemic or renal effects of exogenous angiotensin II in humans

Background Angiotensin II (Ang II) is assumed to play a pathophysiological role in a variety of vascular diseases. Animal studies indicate that these effects are partly attributed to stimulation of endothelin‐1 (ET‐1) release. The aim of the present study was to investigate whether the acute effects of Ang II on systemic and renal haemodynamics in healthy subjects can be influenced by endothelin ETA‐receptor blockade. Design The study design was balanced, randomized, placebo‐controlled, double blind, two‐way cross‐over, in 10 healthy male subjects. Methods Subjects received stepwise increasing intravenous doses of Ang II (0·65, 1·25, 2·5, 5 ng kg−1 min−1 for 15 min per dose level) in the presence or absence of BQ‐123 (60 µg min−1), a specific ETA‐receptor antagonist. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were assessed by the para‐aminohippurate and inulin plasma clearance method, respectively. Renal vascular resistance (RVR) was calculated from mean arterial pressure (MAP) and renal plasma flow. Results Ang II decreased RPF by 34% and GFR by 9% and increased RVR by 94% and MAP by 27% (ANOVA, P