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Previous Volume 338:784-791 March 19, 1998 Number 12 Next

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ABSTRACT

Background Endothelin is a powerful vasoconstrictor peptide derived from the endothelium. We evaluated the contribution of endothelin to blood-pressure regulation in patients with essential hypertension by studying the effect of an endothelin-receptor antagonist, bosentan.

Methods We studied 293 patients with mild-to-moderate essential hypertension. After a placebo run-in period of four to six weeks, patients were randomly assigned to receive one of four oral doses of bosentan (100, 500, or 1000 mg once daily or 1000 mg twice daily), placebo, or the angiotensin-converting–enzyme inhibitor enalapril (20 mg once daily) for four weeks. Blood pressure was measured before and after treatment.

Results As compared with placebo, bosentan resulted in a significant reduction in diastolic pressure with a daily dose of 500 or 2000 mg (an absolute 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 changes in heart rate. Bosentan did not result in activation of the sympathetic nervous system (as determined by measurement of the plasma norepinephrine level) or the renin–angiotensin system (as determined by measurements of plasma renin activity and angiotensin II levels).

Conclusions An endothelin-receptor antagonist, bosentan, significantly lowered blood pressure in patients with essential hypertension, suggesting that endothelin may contribute to elevated blood pressure in such patients. The favorable effect of treatment with bosentan on blood pressure occurred without reflexive neurohormonal activation.

Source Information

From the Clinical Pharmacology Unit, Monash University and Alfred Hospital, Prahran, Victoria, Australia (H.K.); the Department of Medicine, Barzilai Medical Center, Ashkelon, Israel (R.J.V.); the Hypertension Research Unit, Centre Hospitalier Universitaire de Quebec, Ste.-Foy, Que., Canada (Y.L.); and Hoffmann–LaRoche, Basel, Switzerland (M.B., V.C.).

Address reprint requests to Dr. Krum at the Clinical Pharmacology Unit, Monash University, Alfred Hospital, Prahran, Victoria 3181, Australia.

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Bosentan in Essential Hypertension
Haynes W. G., Ferro C. J., Webb D. J., Krämer B. K., Schweda F., Riegger G. A.J., Krum H., Lacourciere Y., Charlon V.
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N Engl J Med 1998; 339:346-347, Jul 30, 1998. Correspondence

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