Key result
Endothelin-1 antagonist BMS-182874 lowers glomerular fibrosis while bosentan and irbesartan blunt tubulointerstitial fibrosis.
Population
Five-week-old Ren-2 transgenic rats (TGRen2) with severe angiotensin II-dependent hypertension
Comparison
Bosentan, irbesartan, BMS-182874, combination of… vs Placebo
Design
Preclinical
Follow-up
4 weeks
Authors
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Preclinical data only; leaves open whether endothelin antagonism reduces renal fibrosis in patients.
p-value: p=<0.001
Endothelin-1 plays a major role in the development of renal fibrosis across glomerular, tubulointerstitial, and perivascular compartments in a model of severe hypertension.
Seccia et al. (2008) studied severe angiotensin II-dependent hypertension. bosentan, irbesartan, BMS-182874, irbesartan plus BMS, and nifedipine vs. placebo was evaluated on Glomerular, tubulointerstitial, and perivascular fibrosis (p=<0.001). Endothelin-1 receptor antagonism with BMS-182874 lowered glomerular fibrosis (P<0.001), while bosentan (P<0.001) and irbesartan (P<0.005) blunted tubulointerstitial fibrosis.