Touyz R M, Deng L Y, Schiffrin E L
MRC Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal, Québec, Canada.
J Cardiovasc Pharmacol. 1995;26 Suppl 3:S193-6.
Endothelin-1 (ET-1) influences vascular function by modulating intracellular free Ca2+ concentration ([Ca2+]i) in smooth muscle. This study investigated the effects of ET-1 on [Ca2+]i and contractile responses in resistance vessels of young prehypertensive (5 week) and adult hypertensive (17 week) spontaneously hypertensive rats (SHRs) and in age-matched normotensive Wistar-Kyoto (WKY) rats. Third-order branches of mesenteric arteries were mounted in a perfusion myograph and maintained at 60 mm Hg. Vessel [Ca2+]i was measured by Fura-2 and contraction was determined using video imaging to record lumen diameter. [Ca2+]i was higher (p < 0.01) in 5- and 17-week SHRs compared with 5- and 17-week WKYs rats. ET-1 increased [Ca2+]i and contractile responses in a dose-dependent manner in all groups. ET-induced [Ca2+]i change and vessel contractility were not significantly different between age-matched SHR and WKY groups, but [Ca2+]i responses were more sensitive in 5- compared with 17-week SHRs. These data demonstrate that ET-1-stimulated [Ca2+]i and contractile responses in resistance arteries are similar in age-matched WKY rats and SHRs and are blunted in adult SHRs compared with young prehypertensive rats. Therefore, ET-1 may not play a major role in the development of hypertension in SHRs.
内皮素-1（ET-1）通过调节平滑肌细胞内游离钙离子浓度（[Ca2+]i）来影响血管功能。本研究调查了ET-1对年轻的高血压前期（5周龄）和成年高血压（17周龄）自发性高血压大鼠（SHR）以及年龄匹配的正常血压Wistar-Kyoto（WKY）大鼠阻力血管中[Ca2+]i和收缩反应的影响。将肠系膜动脉的三级分支安装在灌注肌动描记器中，并维持在60 mmHg。用Fura-2测量血管[Ca2+]i，并使用视频成像记录管腔直径来确定收缩情况。与5周龄和17周龄的WKY大鼠相比，5周龄和17周龄的SHR中[Ca2+]i更高（p < 0.01）。ET-1在所有组中均以剂量依赖性方式增加[Ca2+]i和收缩反应。年龄匹配的SHR组和WKY组之间，ET诱导的[Ca2+]i变化和血管收缩性无显著差异，但与17周龄的SHR相比，5周龄的SHR中[Ca2+]i反应更敏感。这些数据表明，在年龄匹配的WKY大鼠和SHR中，ET-1刺激的阻力动脉中[Ca2+]i和收缩反应相似，与年轻的高血压前期大鼠相比，成年SHR中的反应减弱。因此，ET-1可能在SHR高血压的发生中不发挥主要作用。
