(Hypertension. 1999;34:1254.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Interaction Between Nitric Oxide and Endogenous Vasoconstrictors in Control of Renal Blood Flow
From I. Physiologisches Institut der Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany.
Correspondence to Dr Heimo Ehmke, I. Physiologisches Institut der Ruprecht-Karls Universität, Im Neuenheimer Feld 326, D-69120 Heidelberg, Germany. E-mail ehmke{at}novsrv1.pio1.uni-heidelberg.de
Abstract—The level of renal blood
flow (RBF) is controlled by opposing vasoconstrictor and vasodilator
influences. In a recent investigation in normotensive dogs, we found
that combined blockade of endothelin type A (ETA) receptors
and angiotensin II formation induces marked increases in
RBF that were much larger than the effects of blocking either system
alone. The aim of the present study was to determine the
contribution of nitric oxide (NO) to this vasodilator response.
Experiments were made in 6 conscious, chronically instrumented dogs
subjected to 5 different experimental treatments on separate days.
Blockade of ETA receptors alone by the selective
antagonist LU 135252 had only minor effects on RBF compared
with time-control experiments. Additional blockade of
angiotensin II formation by
angiotensin-converting enzyme inhibition with
trandolaprilat caused a substantial increase of RBF by 
50%. This
vasodilation was entirely suppressed when NO formation was prevented by
inhibition of NO synthase with
NG-nitro-L-arginine methyl ester
HCl. However, when during NO synthase inhibition renal vascular NO
concentrations were clamped at control levels by infusing the NO donor
S-nitroso-N-acetyl-D,L-penicillamine,
the vasodilator response to combined blockade of ETA
receptors and angiotensin II formation was completely
restored (
RBF 60%). These results indicate that the vasodilation
after combined ETA receptor blockade and
angiotensin-converting enzyme inhibition is not mediated by
an increase in NO release but results from the unmasking of the tonic
influence that is normally exerted by constitutively released NO.
Accordingly, the tonic activity of endothelial NO
synthase appears to be of major importance in the
physiological regulation of renal vascular
resistance by determining the vasomotor responses to endothelin and
angiotensin II.
Key Words: endothelin • receptors, endothelin • nitric oxide • renal circulation • renin-angiotensin system
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