Activation of the Fas/Fas ligand pathway in hypertensive renal disease in Dahl/Rapp rats.
BACKGROUND
Hypertensive nephrosclerosis is the second most common cause of end-stage renal failure in the United States. The mechanism by which hypertension produces renal failure is incompletely understood. Recent evidence demonstrated that an unscheduled and inappropriate increase in apoptosis occurred in the Dahl/Rapp rat, an inbred strain of rat that uniformly develops hypertension and hypertensive nephrosclerosis; early correction of the hypertension prevents the renal injury. The present study examined the role of the Fas/FasL pathway in this process.


METHODS
Young male Dahl/Rapp salt-sensitive (S) and Sprague-Dawley rats were fed diets that contained 0.3% or 8.0% NaCl diets. Kidneys were examined at days 7 and 21 of the study.


RESULTS
An increase in Fas and FasL expression was observed in glomerular and tubular compartments of kidneys of hypertensive S rats, whereas dietary salt did not change expression of either of these molecules in normotensive Sprague-Dawley rats. Associated with this increase was cleavage of Bid and activation of caspase-8, the initiator caspase in this apoptotic pathway, by day 21 of the study.


CONCLUSIONS
Augmented expression of apoptotic signaling by the Fas/FasL pathway occurred during development of end-stage renal failure in this model of hypertensive nephrosclerosis.
Sanders
Paul W
PW
Nephrology Research and Training Center, Comprehensive Cancer Center, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA. psanders@uab.edu
Wang
Pei-Xuan
PX
D000818:Animals; D017209:Apoptosis; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism; D053938:DNA Fragmentation; D004195:Disease Models, Animal; D004789:Enzyme Activation; D053222:Fas Ligand Protein; D006973:Hypertension / Q000150:complications / Q000378:metabolism*; D015151:Immunoblotting; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009400:Nephrosclerosis / Q000209:etiology*; D051381:Rats; D020303:Rats, Inbred Dahl; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage; D019014:fas Receptor / Q000378:metabolism*
D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008024:Ligands; D008562:Membrane Glycoproteins; D017673:Sodium Chloride, Dietary; D019014:fas Receptor; C505528:Casp8 protein, rat; D053181:Caspase 8; D020169:Caspases