Contribution of endothelin to renal vascular tone and
autoregulation in the conscious dog.
Berthold, Heike, Klaus M[umlaut]unter, Armin Just, Hartmut R.
Kirchheim, and Heimo Ehmke.
Physiologisches Institut der Ruprecht-Karls-Universit[umlaut]at
Heidelberg, 69120 Heidelberg, Germany and 1 Knoll AG, 67061
Ludwigshafen, Germany
APStracts 5:0197F, 1998.
Exogenous endothelin-1 (ET-1) is a strong vasoconstrictor in the
canine kidney and causes a decrease in renal blood flow (RBF) by
stimulating the ETA receptor subtype. The aim of the present study
was to investigate the role of endogenously generated ET-1 in renal
hemodynamics under physiological conditions. In six conscious
foxhounds the time course of the effects of the selective ETA
receptor antagonist LU 135252 (10 mg/kg iv.) on mean arterial blood
pressure (MAP), heart rate (HR), renal blood flow (RBF), and
glomerular filtration rate (GFR) as well as its effects on renal
autoregulation were examined. LU 135252 increased RBF by 20% (from
270+/-21 ml/min to 323+/-41 ml/min, p<0.05) and HR from 765
beats/min to 978 beats/min (p<0.05), but did not alter MAP, GFR, or
autoregulation of RBF and GFR. Since a number of interactions between
ET-1 and the renin-angiotensin system have been reported previously,
experiments were repeated during angiotensin converting-enzyme (ACE)
inhibition by trandolaprilat (2 mg/kg iv.). When ETA receptor
blockade was combined with ACE inhibition, which by itself had no
effects on renal hemodynamics, marked changes were observed: MAP
decreased from 91+/-4 mmHg to 80+/-5 mmHg (p<0.05), HR increased
from 85+/-5 beats/min to 102+/-11 beats/min (p<0.05), and RBF
increased from 278+/-23 ml/min to 412+/-45 ml/min (p<0.05). In
spite of a pronounced decrease in renal vascular resistance over the
entire pressure range investigated (40-100 mmHg), the capacity of the
kidneys to autoregulate RBF was not impaired. The GFR remained
completely unaffected at all pressure levels. These results
demonstrate that endogenously generated ET-1 contributes
significantly to renal vascular tone, but does not interfere with the
mechanisms of renal autoregulation. If ETA receptors are blocked, the
vasoconstrictor effects of ET-1 in the kidney are compensated for to
a large extent by an augmented influence of ANG II. Thus, ET-1 and
ANG II appear to constitute a major interrelated vasoconstrictor
system in the control of RBF.
Received 20 January 1998; accepted in final form 3 November 1998.
APS Manuscript Number F014-8.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 10 November 1998