内皮素受体拮抗剂对高盐摄入的血管紧张素 II 输注大鼠肾血流动力学的影响。

Effects of endothelin receptor antagonists on renal hemodynamics in angiotensin II-infused rats on high NaCl intake.

机构信息

Department of Molecular and Clinical Medicine/Nephrology, Institute of Medicine, The Sahlgrenska Academy at the University of Gothenburg, Sweden.

出版信息

Kidney Blood Press Res. 2012;36(1):258-67. doi: 10.1159/000343415. Epub 2012 Nov 26.

DOI:10.1159/000343415

PMID:23171921

Abstract

AIM

The aim was to investigate effects of selective endothelin (ET) receptor antagonists on renal hemodynamics and dynamic renal blood flow autoregulation (RBFA) in angiotensin II (Ang II)-infused rats on a high NaCl intake.

METHODS

Sprague-Dawley rats received Ang II (250 ng/kg/min, s.c.) and an 8% NaCl diet for 14 days after which renal clearance experiments were performed. After baseline measurements animals were administered either: (a) saline vehicle; (b) ETA receptor antagonist BQ-123 (30 nmol/kg/min); (c) ETB receptor antagonist BQ-788 (30 nmol/kg/min); or (d) BQ-123 + BQ-788, for six consecutive 20-minute clearance periods.

RESULTS

BQ-123 reduced arterial pressure (AP) and selectively increased outer medullary perfusion versus vehicle (p<0.05). These effects were attenuated or abolished by combined BQ-123 and BQ-788. BQ-788 reduced renal blood flow and increased renovascular resistance (p<0.05). Ang II-infused rats on high NaCl intake showed abnormalities in dynamic RBFA characterized by an impaired myogenic response that were not significantly affected by ET receptor antagonists.

CONCLUSION

In hypertensive Ang II-infused rats on a high-NaCl intake selective ETA antagonism with BQ-123 reduced AP and specifically increased OM perfusion and these effects were dependent on intact ETB receptor stimulation. Furthermore, ET receptor antagonists did not attenuate abnormalities in dynamic RBFA.

摘要

目的

研究选择性内皮素（ET）受体拮抗剂对高盐摄入的血管紧张素 II（Ang II）输注大鼠肾血流动力学和肾血流自动调节（RBFA）的影响。

方法

Sprague-Dawley 大鼠接受 Ang II（250ng/kg/min，皮下注射）和 8%NaCl 饮食 14 天后进行肾清除实验。在基线测量后，动物分别给予：（a）生理盐水载体；（b）ETA 受体拮抗剂 BQ-123（30nmol/kg/min）；（c）ETB 受体拮抗剂 BQ-788（30nmol/kg/min）；或（d）BQ-123+BQ-788，连续 6 个 20 分钟清除期。

结果

BQ-123 降低了动脉压（AP），并选择性地增加了与载体相比的外髓质灌注（p<0.05）。这些作用被 BQ-123 和 BQ-788 的联合使用减弱或消除。BQ-788 降低了肾血流量并增加了肾血管阻力（p<0.05）。高盐摄入的 Ang II 输注大鼠表现出动态 RBFA 的异常，其特征是肌源性反应受损，而 ET 受体拮抗剂对其没有明显影响。