血管加压素和内皮素-1对自发性高血压大鼠加压小动脉血管收缩和钙反应的不同影响。

Differential effects of vasopressin and endothelin-1 on vascular contractile and calcium responses in pressurized small arteries from spontaneously hypertensive rats.

作者信息

Touyz R M, Deng L Y, Li J S, Schiffrin E L

机构信息

MRC Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montréal, University of Montréal, Québec, Canada.

出版信息

J Hypertens. 1996 Aug;14(8):983-91.

PMID:8884553

Abstract

OBJECTIVE

To investigate the effects of vasopressin and endothelin-1 on the intracellular free calcium concentration ([Ca2+]i) and on contractile responses in endothelium-denuded resistance vessels of prehypertensive (5-week-old) and adult hypertensive (17-week-old) spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) rats.

METHODS

Segments (2 mm long) of third-order branches of small mesenteric arteries were mounted in a perfusion myograph and maintained at 60 mmHg pressure. Endothelium was removed by intraluminal passage of air. The vessel [Ca2+]i was measured by fura-2 fluorescence and contraction was determined using a video imaging system to record lumen diameter.

RESULTS

Lumen diameter was significantly smaller in 5-and 17-week-old SHR than it was in age-matched WKY rats (5 week-old SHR versus WKY rats: 178 +/- 4.0 versus 195 +/- 4.3 microns; 17-week-old SHR versus WKY rats: 168 +/- 7.0 versus 230 +/- 3.1 microns). The basal [Ca2+]i was significantly higher in 5- and 17-week-old SHR than it was in age-matched WKY rats. Infusions of vasopressin and endothelin-1 increased [Ca2+]i and contractile responses in a dose-dependent manner in all groups. The vasopressin-induced change in [Ca2+]i was significantly greater in 5- and 17-week-old SHR than in age-matched controls. The sensitivity of [Ca2+]i to vasopressin was increased in adult SHR compared with WKY rats (pD2 9.0 +/- 0.1 in SHR, 8.2 +/- 0.3 in WKY rats). Vasopressin-stimulated contractile responses were increased in adult SHR. The endothelin-1-induced change in [Ca2+]i did not differ between WKY rats and SHR. The contractility of vessels in response to endothelin-1 infusion was similar in age-matched groups.

CONCLUSIONS

Endothelin-1-induced changes in [Ca2+]i and contractile responses in small arteries are similar in age-matched WKY rats and SHR, whereas responses to vasopressin are significantly enhanced in SHR compared with WKY rats. Thus [Ca2+]i signalling for vasopressin is more active than is that for endothelin-1. Vasopressin but not endothelin-1 might play a role in the development of hypertension in SHR.

摘要

目的

研究血管加压素和内皮素-1对高血压前期（5周龄）和成年高血压（17周龄）自发性高血压大鼠（SHR）以及年龄匹配的Wistar-Kyoto（WKY）大鼠去内皮阻力血管细胞内游离钙浓度（[Ca2+]i）和收缩反应的影响。

方法

取肠系膜小动脉三级分支的节段（2毫米长），安装在灌注肌动描记器中，维持在60 mmHg压力。通过腔内通气去除内皮。用fura-2荧光法测量血管[Ca2+]i，并用视频成像系统记录管腔直径来测定收缩情况。

结果

5周龄和17周龄的SHR管腔直径明显小于年龄匹配的WKY大鼠（5周龄SHR与WKY大鼠比较：178±4.0对195±4.3微米；17周龄SHR与WKY大鼠比较：168±7.0对230±3.1微米）。5周龄和17周龄的SHR基础[Ca2+]i明显高于年龄匹配的WKY大鼠。在所有组中，血管加压素和内皮素-1的输注均以剂量依赖性方式增加[Ca2+]i和收缩反应。5周龄和17周龄的SHR中血管加压素诱导的[Ca2+]i变化明显大于年龄匹配的对照组。与WKY大鼠相比，成年SHR中[Ca2+]i对血管加压素的敏感性增加（SHR中pD2为9.0±0.1，WKY大鼠中为8.2±0.3）。成年SHR中血管加压素刺激的收缩反应增加。WKY大鼠和SHR之间内皮素-1诱导的[Ca2+]i变化无差异。年龄匹配组中，血管对内皮素-1输注的收缩性相似。