Sharifi A M, Schiffrin E L
MRC Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montréal, University of Montréal, QC, Canada.
Can J Physiol Pharmacol. 1996 Aug;74(8):934-9.
The effects of endothelin-1 (ET-1), a nonselective ETA and ETB receptor agonist, and sarafotoxin S6c, a selective ETB agonist, were investigated in the presence and absence of BQ123 and BQ788, ETA- and ETB-selective antagonists, respectively, in rat mesenteric small arteries, using a perfusion pressurized arteriograph in which segments of vessels were cannulated and exposed to constant pressure and flow. ET-1 (10(-13)-10(-7) M) induced vasoconstriction in both intact and endothelium-denuded arteries in a concentration-dependent manner. BQ123 (10(-7) and 10(-6) M) inhibited the effect of ET-1, displacing the concentration-response curve to the right in a concentration-dependent manner. The effect of ET-1 was not significantly affected by BQ788 (10(-7) and 10(-6) M), a selective antagonist of ETB receptors. Sarafotoxin S6c (10(-11)-10(-7) M) also induced a slight concentration-dependent vasoconstriction. The effect of sarafotoxin S6c (10(-8) M) was inhibited by the ETB-selective antagonist BQ788 (10(-7) M), but was not significantly changed by BQ123 (10(-7) M). Vasoconstriction induced by sarafotoxin S6c (10(-8) M) in a single bolus concentration was significantly greater than the contraction induced by the same concentration as part of a cumulative concentration-response curve, indicating desensitization or downregulation of ETB receptors during the latter. Repeated application of single concentrations of sarafotoxin S6c (10(-8) M) caused progressively smaller contraction of arteries. These results show the existence of both ETA and ETB vasoconstrictor receptors located on smooth muscle of small arteries. They also show that ETB receptors induce a smaller constrictor effect, and rapidly undergo desensitization after sustained or repeated activation.
使用灌注加压动脉造影仪，将大鼠肠系膜小动脉段插管并暴露于恒定压力和流量下，分别在存在和不存在ETA和ETB选择性拮抗剂BQ123和BQ788的情况下，研究了非选择性ETA和ETB受体激动剂内皮素-1（ET-1）以及选择性ETB激动剂铃蟾毒素S6c的作用。ET-1（10^(-13)-10^(-7)M）以浓度依赖性方式在完整动脉和内皮剥脱动脉中均诱导血管收缩。BQ123（10^(-7)和10^(-6)M）抑制ET-1的作用，以浓度依赖性方式将浓度-反应曲线向右移动。ET-1的作用不受ETB受体选择性拮抗剂BQ788（10^(-7)和10^(-6)M）的显著影响。铃蟾毒素S6c（10^(-11)-10^(-7)M）也诱导轻微的浓度依赖性血管收缩。铃蟾毒素S6c（10^(-8)M）的作用被ETB选择性拮抗剂BQ788（10^(-7)M）抑制，但未被BQ123（10^(-7)M）显著改变。单次推注浓度为10^(-8)M的铃蟾毒素S6c诱导的血管收缩明显大于作为累积浓度-反应曲线一部分的相同浓度诱导的收缩，表明后者期间ETB受体脱敏或下调。重复应用单一浓度的铃蟾毒素S6c（10^(-8)M）导致动脉收缩逐渐减小。这些结果表明，小动脉平滑肌上存在ETA和ETB血管收缩受体。它们还表明，ETB受体诱导的收缩作用较小，并且在持续或重复激活后迅速发生脱敏。
