Treatment of cardiovascular changes in renal failure--ACE inhibition, endothelin receptor blockade or a combination of both strategies?
ACE-I and specific ETA receptor blockade comparably prevented the development of structural cardiovascular alterations such as LVH, myocardial interstitial expansion and wall thickening of intramyocardial and extracardiac arteries in experimental renal failure. However, the decrease in myocardial capillary supply and the concomitant increase in intercapillary distance could only be prevented by ETA receptor antagonism. These capillary changes which have been shown to occur in experimental renal failure as well as in uraemic patients play an important role in the pathogenesis of reduced cardiac ischaemia tolerance in renal failure. The data argue for a potential role of the local renin-angiotensin system as well as of the ET system in the pathogenesis of cardiovascular changes in renal failure and for ET receptor blockade as a new therapeutic option in the treatment of these alterations. In particular, myocardial capillary supply, which is particularly important for ischaemia tolerance in renal failure, seems to be modulated and regulated predominantly by ET-1. In contrast to what was found with respect to structural and functional changes of the kidney in various experimental models of renal damage, a combination therapy--at least in the doses used--does not seem to provide additional benefit in the prevention of cardiovascular changes compared with the respective monotherapies.
Amann
K
K
Department of Pathology, University of Heidelberg, Germany.
Münter
K
K
Wagner
J
J
Balajew
V
V
Hergenröder
S
S
Mall
G
G
Ritz
E
E
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects*; D004359:Drug Therapy, Combination; D065128:Endothelin Receptor Antagonists; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A; D051437:Renal Insufficiency / Q000188:drug therapy*
D000806:Angiotensin-Converting Enzyme Inhibitors; D065128:Endothelin Receptor Antagonists; D044022:Receptor, Endothelin A