The effect of an endothelin-receptor antagonist, bosentan, on blood pressure in patients with essential hypertension
The effect of an endothelin-receptor antagonist, bosentan, on blood pressure in patients with essential hypertension
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DOI：
10.1056/nejm199803193381202
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发表时间：
1998-03-19
影响因子：
158.5
通讯作者：
Charlon, V
中科院分区：
文献类型：
--
作者：
Krum, H;Viskoper, RJ;Charlon, V
背景内皮素是一种来源于血管内皮细胞的强大的血管收缩多肽。我们通过研究内皮素受体拮抗剂波生坦对高血压患者血压调节的影响，来评价内皮素在高血压患者血压调节中的作用。经过4至6周的安慰剂磨合期后，患者被随机分配到四种剂量的口服波生坦(100、500或1000毫克，每天一次或1000毫克，每天两次)、安慰剂或血管紧张素转换酶抑制剂依那普利(每天20毫克)中的一种，为期四周。结果与安慰剂相比，波生坦每日剂量为500或2000 mg时，舒张压显著降低(每一剂量的绝对降幅为5.7 mm Hg)，与依那普利的降幅(5.8 mm Hg)相似，但对心率无明显影响。波生坦不能激活交感神经系统(通过测量血浆去甲肾上腺素水平来确定)或肾素-血管紧张素系统(通过测量血浆肾素活性和血管紧张素II水平来确定)，结论内皮素受体拮抗剂波生坦可显著降低高血压病患者的血压，提示内皮素可能与高血压患者的血压升高有关。波生坦治疗血压的良好效果发生在没有反射性神经激素激活的情况下，(C)1998，马萨诸塞州医学会。
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, (C) 1998, Massachusetts Medical Society.