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Endothelin ETA receptor‐subtype specific antagonism does not mitigate the acute systemic or renal effects of exogenous angiotensin II in humans
Author(s) -
BayerleEder M.,
Langenberger H.,
Pleiner J.,
Polska E.,
Mensik C.,
Eichler H.G.,
Wolzt M.,
Schmetterer L.
Publication year - 2002
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.2002.00974.x
Subject(s) - renal blood flow , angiotensin ii , medicine , endothelin receptor , endocrinology , renal function , vascular resistance , effective renal plasma flow , hemodynamics , renal circulation , filtration fraction , kidney , endothelin 1 , mean arterial pressure , renin–angiotensin system , blood pressure , receptor , heart rate
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 ET A ‐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 ET A ‐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 < 0·001 vs. baseline, for all parameters). BQ‐123 did not alter these renal and systemic haemodynamic responses to a significant degree. In addition, BQ‐123 had no significant haemodynamic effect under baseline conditions. Conclusions Short‐term increase of circulating Ang II levels causes systemic and renal pressor effects, which are not mitigated by endothelin ET A ‐receptor blockade. This suggests that the pressor response to Ang II cannot be accounted for by the acute release of vasoactive ET‐1.