Touyz R M, Deng L Y, Schiffrin E L
MRC Multidisciplinary Research Group on Hypertension, University of Montreal, Quebec, Canada.
Hypertension. 1995 Dec;26(6 Pt 2):1041-5. doi: 10.1161/01.hyp.26.6.1041.
Endothelin-1 elicits vasoconstrictor responses through endothelin subtype A receptors, which are located on vascular smooth muscle cells, and vasodilator responses through endothelin subtype B receptors, which occur predominantly on endothelial cells. Endothelin subtype B receptors also may be present on vascular smooth muscle cells, in which they may mediate vasoconstriction. The aims of this study were to determine the presence of vascular smooth muscle vasoconstrictor endothelin subtype B receptors in mesenteric resistance arteries and to assess whether endothelin subtype B receptor-mediated responses differ between spontaneously hypertensive rats and Wistar-Kyoto rats. Contractile responses to the endothelin subtype B receptor agonist sarafotoxin S6c and endothelin-1 were measured simultaneously with [Ca2+]i in endothelium-denuded mesenteric resistance arteries from adult spontaneously hypertensive rats and Wistar-Kyoto rats. To simulate in vivo conditions matched as closely as possible to in vitro conditions, vessels were mounted in a vessel flow chamber in which intraluminal pressure was maintained at 60 mm Hg. Contraction was determined by video imaging to record lumen diameter, and [Ca2+]i was measured by the fura 2 method. Basal [Ca2+]i was significantly higher (P < .01) in hypertensive (170 +/- 4 nmol/L) compared with normotensive rats (134 +/- nmol/L). The endothelin subtype B receptor agonist sarafotoxin S6c increased [Ca2+]i in a concentration-dependent manner. Sarafotoxin S6c-induced [Ca2+]i and contractile responses were significantly lower in hypertensive compared with normotensive rats. These data demonstrate that endothelin subtype B receptors are present in vascular smooth muscle of small arteries and that endothelin subtype B receptor-mediated vasoconstriction occurs through intracellular calcium signaling pathways.(ABSTRACT TRUNCATED AT 250 WORDS)
内皮素-1通过位于血管平滑肌细胞上的内皮素A型受体引发血管收缩反应，并通过主要存在于内皮细胞上的内皮素B型受体引发血管舒张反应。内皮素B型受体也可能存在于血管平滑肌细胞上，在这些细胞中它们可能介导血管收缩。本研究的目的是确定肠系膜阻力动脉中血管平滑肌血管收缩性内皮素B型受体的存在，并评估自发性高血压大鼠和Wistar-Kyoto大鼠之间内皮素B型受体介导的反应是否存在差异。在成年自发性高血压大鼠和Wistar-Kyoto大鼠去内皮的肠系膜阻力动脉中，同时测量对内皮素B型受体激动剂沙拉新S6c和内皮素-1的收缩反应以及[Ca2+]i。为了尽可能紧密地模拟体内条件与体外条件相匹配，将血管安装在血管流动室中，其中管腔内压力维持在60 mmHg。通过视频成像记录管腔直径来确定收缩，并通过fura 2方法测量[Ca2+]i。与正常血压大鼠（134±nmol/L）相比，高血压大鼠（170±4 nmol/L）的基础[Ca2+]i显著更高（P<0.01）。内皮素B型受体激动剂沙拉新S6c以浓度依赖性方式增加[Ca2+]i。与正常血压大鼠相比，高血压大鼠中沙拉新S6c诱导的[Ca2+]i和收缩反应显著更低。这些数据表明，内皮素B型受体存在于小动脉的血管平滑肌中，并且内皮素B型受体介导的血管收缩通过细胞内钙信号通路发生。（摘要截断于250字）
