Key result
Selective ET(A) blockade with LU 135252 reduces rhEPO-induced hypertension by ~27 mmHg in uremic rats.
Why the study?
The role of endothelin-1 receptor blockade in preventing hypertension progression in renal failure rats treated with recombinant human erythropoietin was unclear, including the differential effects of selective ET(A) versus nonselective ET(A)/ET(B) antagonists.
Does selective ET(A) or nonselective ET(A)/ET(B) receptor blockade prevent the progression of hypertension in renal failure rats receiving rhEPO?
Does selective ET(A) or nonselective ET(A)/ET(B) receptor blockade prevent the progression of hypertension in renal failure rats receiving rhEPO?
Absolute Event Rate: 160% vs 187%
p-value: p=<0.05
Selective ET(A) receptor blockade, but not nonselective ET(A)/ET(B) blockade, prevents the aggravation of hypertension in uremic rats treated with recombinant human erythropoietin.
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Selective ET(A) blockade merits human trials in rhEPO-treated CKD; leaves open clinical translation.
Brochu et al. (1999) studied Renal failure with erythropoietin-induced hypertension (animal model). Selective ET(A) receptor antagonist LU 135252 or nonselective ET(A)/ET(B) receptor antagonist bosentan vs. Vehicle was evaluated on Systolic blood pressure (p=<0.05). Treatment with the selective ET(A) receptor antagonist LU 135252 attenuated rhEPO-induced hypertension in uremic rats (160+/-7 vs 187+/-9 mmHg, P<0.05), whereas bosentan did not.
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