Glomerular endothelin receptors during initiation and maintenance of ischemic acute renal failure in rats.
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.
Wilkes
B M
BM
Department of Medicine, North Shore University Hospital, Manhasset, New York 11030.
Pearl
A R
AR
Mento
P F
PF
Maita
M E
ME
Macica
C M
CM
Girardi
E P
EP
D058186:Acute Kidney Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D016232:Endothelins / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007261:Infusions, Intra-Arterial; D007511:Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure*; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017466:Receptors, Endothelin
D016232:Endothelins; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin