Regulation of intrarenal blood flow in experimental heart failure:
role of endothelin and nitric oxide.
Abassi, Zaid, Konstantin Gurbanov, Irith Rubinstein, Ori S. Better,
Aaron Hoffman, and Joseph Winaver.
Department of Physiology and Biophysics, Faculty of Medicine,
Technion-Israel Institute of Technology,, and department of vascular
surgery, Rambam Medical Center, Haifa 31096, Israel
APStracts 5:0004F, 1998.
Congestive heart failure (CHF) is associated with a marked decrease in
cortical blood flow (CBF) and preservation of medullary blood flow
(MBF). In the present study we tested the hypothesis that changes in
the endothelin (ET) and nitric oxide (NO) systems in the kidney may
contribute to the altered intrarenal hemodynamics in rats with aorto
-caval fistula, an experimental model of CHF. CBF and MBF were
measured simultaneously by laser-Doppler flowmetry in control and
rats with compensated and decompensated CHF. As previously reported
(Am. J. Physiol. 271; F1166, 1996), administration of ET-1 in control
rats produced a sustained cortical vasoconstriction and a transient
medullary vasodilatory response. In rats with decompensated CHF the
cortical vasoconstriction was severely blunted, whereas ET-1 induced
medullary vasodilatation was significantly prolonged. This prolonged
response was mimicked by IRL-1620, a specific ET_B_ agonist, and
partially abolished by NO synthase (NOS) blockade. In line with these
findings, the expression of ET-1, ET_A_ and ET_B_ receptors, and of
endothelial (e) NOS, assessed by reverse transcription polymerase
chain reaction, and eNOS immunoreactivity, assessed by Western
blotting, were significantly higher in the medulla than in cortex.
Moreover, the expression of ET-1 mRNA in the cortex and of eNOS mRNA
both in cortex and medulla increased in proportion to the severity of
heart failure. These findings indicate that CHF is associated with
altered regulation of intrarenal blood flow which reflects
alterations in the expression and activity of the ET and NO systems.
It is further suggested that exaggerated NO activity in the medulla
contributes to the preservation of MBF in face of cortical
vasoconstriction in CHF.
Received 27 May 1997; accepted in final form 18 December 1997.
APS Manuscript Number F175-7.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 9 January 1998