Rapid Communication Effect of a Nonselective Endothelin Antagonist on Vascular Remodeling in Deoxycorticosterone Acetate-Salt Hypertensive Rats Evidence for a Role of Endothelin in Vascular Hypertrophy

Abstract We have previously shewn that the endothelin content in arteries of deoxycorticosterone acetate (DOCA)-salt hypertensive rats is increased. We designed this study to examine, using the new orally active nonselective endothelin receptor antagonist bosentan, whether this increase in vascular endothelin may contribute to elevated blood pressure and vascular hypertrophy in DOCA-salt hypertensive rats. Rats received bosentan (100 mg/kg body wt per day) for 3 weeks mixed with their food. Systolic blood pressure of DOCA-salt hypertensive rats rose to 197±5 mm Hg, and that of bosentan-treated DOCA-salt hypertensive rats was 177±4 mm Hg (P<.01). Mesenteric resistance arteries were studied on a wire myograph. The media width, ratio of media width to lumen diameter, and cross-sectional area of the media of resistance arteries of bosentan-treated DOCA-salt hypertensive rat