Early-onset endothelin receptor blockade in hypertensive heterozygous Ren-2 rats

Male heterozygous Ren-2 transgenic rats and Hannover Sprague-Dawley rats fed a normal or high-salt diet were either untreated or treated with the nonselective receptor ETA/ETB receptor blocker bosentan or the selective ETA receptor blocker, ABT-627, known as atrasentan. Survival rate was partly increased by bosentan and fully normalized by atrasentan. Bosentan did not significantly influence the course of hypertension in TGR, whereas atrasentan significantly decreased BP on both diets. Atrasentan substantially reduced proteinuria, cardiac hypertrophy, glomerulosclerosis and left ventricular ET-1 tissue concentration on both diets. Our data indicate that ETA receptor blockade is superior to nonselective blockade in attenuating hypertension, end-organ damage and improving survival rate.