Rajagopalan S, Laursen J B, Borthayre A, Kurz S, Keiser J, Haleen S, Giaid A, Harrison D G
Department of Medicine, Emory University School of Medicine, Atlanta, Ga 30322, USA.
Hypertension. 1997 Jul;30(1 Pt 1):29-34. doi: 10.1161/01.hyp.30.1.29.
Experiments in cultured vascular smooth muscle cells have shown that angiotensin II (Ang II) stimulates expression of endothelin-1. We sought to examine role of endothelin-1 in the effects of Ang II in vivo. Ang II infusion in rats (0.7 mg/kg per day for 5 days) was associated with marked increases in vascular smooth muscle endothelin-1 levels, as assessed by immunostaining. Administration of the selective endothelin type A (ET(A)) receptor antagonist PD 155080 (50 mg/kg per day) abrogated the hypertensive response to a 5-day infusion of Ang II (0.7 mg/kg per day), as did losartan (25 mg/kg per day). ET(A) receptor blockade during Ang II-mediated hypertension was associated with marked elevations of plasma endothelin-1 levels. Ang II-mediated hypertension was associated with heightened vascular responsiveness to a variety of vasoconstrictor agents except endothelin-1. Blockade of ET(A) receptor invariably corrected this vasoconstrictor hyperresponsiveness. We conclude that some of the vascular effects of Ang II thought to be unique to this hormone are likely mediated by endothelin-1.
在培养的血管平滑肌细胞中进行的实验表明，血管紧张素II（Ang II）可刺激内皮素-1的表达。我们试图研究内皮素-1在Ang II体内作用中的作用。通过免疫染色评估，给大鼠输注Ang II（0.7毫克/千克/天，持续5天）与血管平滑肌内皮素-1水平的显著升高有关。给予选择性A型内皮素（ET(A)）受体拮抗剂PD 155080（50毫克/千克/天）可消除对5天输注Ang II（0.7毫克/千克/天）的高血压反应，氯沙坦（25毫克/千克/天）也有同样效果。在Ang II介导的高血压期间阻断ET(A)受体与血浆内皮素-1水平的显著升高有关。Ang II介导的高血压与血管对多种血管收缩剂（内皮素-1除外）的反应性增强有关。阻断ET(A)受体总是能纠正这种血管收缩剂高反应性。我们得出结论，Ang II的一些被认为是该激素特有的血管效应可能是由内皮素-1介导的。
