PMID- 11057440
OWN - NLM
STAT- MEDLINE
DCOM- 20010208
LR  - 20190822
IS  - 0263-6352 (Print)
IS  - 0263-6352 (Linking)
VI  - 18
IP  - 10
DP  - 2000 Oct
TI  - Improvement of renal dysfunction in rats with chronic heart failure after 
      myocardial infarction by treatment with the endothelin A receptor antagonist, LU 
      135252.
PG  - 1507-14
AB  - OBJECTIVE: To investigate the role of an activated endothelin system in the renal 
      dysfunction observed in chronic heart failure after myocardial infarction. 
      METHODS: In rats with heart failure after myocardial infarction and in 
      sham-operated animals (Sham), we investigated the effect on renal function of 
      long-term oral treatment with the selective endothelin A (ETA) receptor 
      antagonist, LU 135252 (30 mg/kg per day; groups MI/LU and Sham/LU) or placebo 
      (groups MI/P, Sham/P). Only animals with extensive myocardial infarction (at 
      least 46% of the left ventricle) were included in the study. Infarct size was 
      matched between groups MI/P and MI/LU. Endogenous creatinine clearance, 
      fractional sodium excretion, and plasma and urinary concentrations of endothelin 
      were determined 12 weeks after myocardial infarction. RESULTS: Endogenous 
      creatinine clearance was significantly lower in group MI/P than in group Sham/P 
      (MI/P: 0.64 +/- 0.05, Sham/P: 0.81 +/- 0.04 ml/min per 100 g body weight; P= 0.01 
      (means +/- SEM)). Treatment with LU 135252 completely prevented the decline in 
      creatinine clearance in rats with chronic myocardial infarction (MI/LU: 0.98 +/- 
      0.21; Sham/LU: 0.83 +/- 0.10). Fractional sodium and protein excretion did not 
      differ among the four groups. Group MI/P had a marked increase in plasma 
      endothelin concentrations, which was not affected by treatment with LU 135252. 
      Urinary endothelin excretion was significantly lower in group MI/P than in group 
      Sham/P. In the treatment groups, no difference could be observed between animals 
      that had suffered myocardial infarction and the sham-operated group, although LU 
      135252 markedly increased the urinary excretion of endothelin. CONCLUSION: Our 
      data demonstrate a restoration of impaired renal function in chronic ischaemic 
      heart failure by treatment with the selective ETA receptor antagonist, LU 135252. 
      These results offer a promising therapeutic option for the treatment of renal 
      insufficiency in patients with chronic heart failure.
FAU - Bauersachs, J
AU  - Bauersachs J
AD  - II Medizinische Universitatsklinik Wurzburg, Germany. 
      j.bauersachs@medizin.uni-wuerzburg.de
FAU - Braun, C
AU  - Braun C
FAU - Fraccarollo, D
AU  - Fraccarollo D
FAU - Widder, J
AU  - Widder J
FAU - Ertl, G
AU  - Ertl G
FAU - Schilling, L
AU  - Schilling L
FAU - Kirchengast, M
AU  - Kirchengast M
FAU - Rohmeiss, P
AU  - Rohmeiss P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Hypertens
JT  - Journal of hypertension
JID - 8306882
RN  - 0 (Endothelin Receptor Antagonists)
RN  - 0 (Endothelins)
RN  - 0 (Phenylpropionates)
RN  - 0 (Pyrimidines)
RN  - 0 (Receptor, Endothelin A)
RN  - 0 (Receptors, Endothelin)
RN  - 33JD57L6RW (darusentan)
SB  - IM
MH  - Animals
MH  - Chronic Disease
MH  - *Endothelin Receptor Antagonists
MH  - Endothelins/metabolism
MH  - Heart Failure/*drug therapy/physiopathology
MH  - Kidney/*drug effects/pathology/physiopathology
MH  - Male
MH  - Myocardial Infarction/complications/*drug therapy
MH  - Phenylpropionates/*therapeutic use
MH  - Pyrimidines/*therapeutic use
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, Endothelin A
MH  - Receptors, Endothelin/physiology
MH  - Renal Artery/drug effects/physiopathology
MH  - Vasodilation/drug effects
EDAT- 2000/11/01 11:00
MHDA- 2001/03/03 10:01
CRDT- 2000/11/01 11:00
PHST- 2000/11/01 11:00 [pubmed]
PHST- 2001/03/03 10:01 [medline]
PHST- 2000/11/01 11:00 [entrez]
AID - 10.1097/00004872-200018100-00020 [doi]
PST - ppublish
SO  - J Hypertens. 2000 Oct;18(10):1507-14. doi: 10.1097/00004872-200018100-00020.