Nephroprotective effects of the endothelin ETA receptor antagonist darusentan in salt-sensitive genetic hypertension

Lars Rothermund, Tobias Traupe, Maike Dieterich, Peter Kossmehl, Chana Yagil, Yoram Yagil, Reinhold Kreutz

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


We tested the effect of selective endothelin ETA receptor blockade on the development renal damage in the Sabra rat model of genetic salt-sensitivity. Animals from the salt-sensitive (SBH/y) and salt-resistant strains (SBN/y) were either salt-loaded with deoxycorticosterone acetate and salt (DOCA) or fed a normal diet. Additional salt-loaded groups were also treated with the selective ETA antagonist darusentan (DA). Salt-loading in SBH/y increased systolic blood pressure by 75 mm Hg and urinary albumin excretion 23-fold (P<0.0001). Darusentan attenuated the rise of systolic blood pressure (50%) and urinary albumin excretion (63%, P<0.01, respectively). Salt-loading in SBH/y was associated with significant increased osteopontin mRNA expression as well as glomerulosclerosis and tubulointerstitial damage in the kidney (P<0.05, respectively). This was either significantly reduced or normalized by darusentan (P<0.05, respectively). Thus, darusentan confers a significant renal protection in the Sabra model of salt-sensitive hypertension.

Original languageEnglish
Pages (from-to)209-216
Number of pages8
JournalEuropean Journal of Pharmacology
Issue number3
StatePublished - 16 May 2003


  • Endothelin
  • Genetic
  • Hypertension
  • Kidney
  • Rat
  • Salt


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