总外周电导介导非肽类混合内皮素受体拮抗剂对醋酸去氧皮质酮盐性高血压大鼠的降压作用。

Total peripheral conductance mediates antihypertensive effect of nonpeptide mixed endothelin receptor antagonist in deoxycorticosterone acetate-salt hypertensive rats.

作者信息

Yu M, Gopalakrishnan V, McNeill J R

机构信息

Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.

出版信息

Am J Hypertens. 1999 Aug;12(8 Pt 1):845-8. doi: 10.1016/s0895-7061(99)00055-2.

DOI:10.1016/s0895-7061(99)00055-2

PMID:10480481

Abstract

The relative contribution of cardiac output (CO) and total peripheral conductance (TPC) to the changes in blood pressure (BP) evoked by an intravenous injection of bosentan, a nonpeptide mixed endothelin (ET) antagonist, were investigated in conscious unrestrained deoxycorticosterone acetate (DOCA)-salt hypertensive rats and sham-control rats. Blood pressure was recorded by radiotelemetry devices and CO by ultrasonic transit-time flow probes. Bosentan significantly reduced BP (from 141 +/- 3 to 111 +/- 3 mm Hg) and increased TPC (from 1.19 +/-0.1 to 1.72 +/- 0.2 mL/min/kg/mm Hg) in DOCA-salt hypertensive rats, but not in sham rats. An increase in CO opposed the BP-lowering effect of the antagonist. The results demonstrate that the role of ET receptors in the maintenance of the hypertensive state in the DOCA-salt model of hypertension is exerted at the level of the resistance vessels and not on factors that regulate cardiac output.

摘要

在清醒自由活动的醋酸脱氧皮质酮（DOCA）-盐高血压大鼠和假手术对照大鼠中，研究了心输出量（CO）和总外周电导（TPC）对静脉注射波生坦（一种非肽类混合内皮素（ET）拮抗剂）引起的血压（BP）变化的相对贡献。通过无线电遥测装置记录血压，通过超声传输时间流量探头记录心输出量。波生坦可显著降低DOCA-盐高血压大鼠的血压（从141±3降至111±3 mmHg），并增加TPC（从1.19±0.1增至1.72±0.2 mL/min/kg/mm Hg），但对假手术大鼠无此作用。心输出量的增加对抗了拮抗剂的降压作用。结果表明，ET受体在DOCA-盐高血压模型中维持高血压状态的作用是在阻力血管水平发挥的，而不是在调节心输出量的因素上。