THE EFFECT OF AN ENDOTHELIN-RECEPTOR ANTAGONIST, BOSENTAN, ON BLOOD-PRESSURE IN PATIENTS WITH ESSENTIAL-HYPERTENSION

Background Endothelin is a powerful vasoconstrictor peptide derived fr om the endothelium. We evaluated the contribution of endothelin to blo od-pressure regulation in patients with essential hypertension by stud ying the effect of an endothelin-receptor antagonist, bosentan. Method s We studied 293 patients with mild-to-moderate essential hypertension . After a placebo run-in period of four to six weeks, patients were ra ndomly assigned to receive one of four oral doses of bosentan (100, 50 0, or 1000 mg once daily or 1000 mg twice daily), placebo, or the angi otensin-converting-enzyme inhibitor enalapril (20 mg once daily) for f our weeks. Blood pressure was measured before and after treatment. Res ults As compared with placebo, bosentan resulted in a significant redu ction in diastolic pressure with a daily dose of 500 or 2000 mg (an ab solute reduction of 5.7 mm Hg at each dose), which was similar to the reduction with enalapril (5.8 mm Hg), There were no significant change s in heart rate. Bosentan did not result in activation of the sympathe tic nervous system (as determined by measurement of the plasma norepin ephrine level) or the renin-angiotensin system (as determined by measu rements of plasma renin activity and angiotensin II levels), Conclusio ns An endothelin-receptor antagonist, bosentan, significantly lowered blood pressure in patients with essential hypertension, suggesting tha t endothelin may contribute to elevated blood pressure in such patient s. The favorable effect of treatment with bosentan on blood pressure o ccurred without reflexive neurohormonal activation, (C) 1998, Massachu setts Medical Society.