AJP - Renal Physiology, Vol 260, Issue 1 110-F118, Copyright © 1991 by American Physiological Society
Glomerular endothelin receptors during initiation and maintenance of ischemic acute renal failure in rats
B. M. Wilkes, A. R. Pearl, P. F. Mento, M. E. Maita, C. M. Macica and E. P. Girardi
Department of Medicine, North Shore University Hospital, Manhasset, New York 11030.
Glomerular endothelin (ET) receptors were studied in normal Sprague-Dawley
rats and in rats with ischemic acute renal failure (ARF) induced by a
60-min occlusion of the left renal artery (right kidney intact). In normal
rats ET bound to specific glomerular receptor sites [equilibrium affinity
constant (Kd), 46.6 +/- 5.8 pM; receptor number (Ro), 1,167 +/- 160 fmol/mg
(n = 7)]. ET infusion (90 ng.kg-1.min-1, intra-arterially) raised mean
arterial pressure by 32 +/- 4 mmHg, lowered renal blood flow (RBF) by 62%
and glomerular filtration rate (GFR) by 49%, and reduced the number of
glomerular ET receptor sites by 62%. Reduced ET binding could not be
explained by prior occupancy, because acid treatment (which dissociates
bound ET from its receptors) did not increase receptor number. If elevated
ET levels contributed to decreased RBF and GFR in ARF, glomerular ET
receptors would be expected to down-regulate. In rats with ischemic ARF
there were no differences in the number or affinity of glomerular ET
receptors in the clamped or contralateral kidneys. Additional studies
demonstrated that the downregulation response to ET infusion was intact in
ARF. The data demonstrate that glomerular ET receptors are unaltered in
ischemic ARF and do not support a role for increased glomerular ET in the
alterations of renal hemodynamics in this model.
