Grammas P, Diglio C, Giacomelli F, Wiener J
Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan 48201.
J Cardiovasc Pharmacol. 1989 Feb;13(2):227-32. doi: 10.1097/00005344-198902000-00008.
The objective of this study was to characterize angiotensin II (AII) receptors in cerebral capillary endothelium and to examine whether the first step in AII responsiveness, namely AII receptor binding, is aberrant in cerebral microvessels obtained from adult spontaneously hypertensive rats (SHR). The binding of [3H]angiotensin II to isolated cerebrocortical microvessels from Sprague-Dawley, Wistar-Kyoto, and SHR rats was used to characterize AII receptors on these vessels. Kinetic experiments yielded an equilibrium-derived Kd (dissociation rate constant/association rate constant) very close to that obtained from Scatchard analysis of saturation binding data. The data indicated that the two normotensive control strains exhibited comparable AII receptor affinity and binding capacity. In contrast, experiments with microvessels from adult SHR indicated a significantly higher Bmax for AII receptors relative to controls. Although experiments assessing functional endothelial alterations in the SHR to AII remain to be performed, the increase in AII receptor number suggests that an abnormality in vascular AII responsiveness may play an important role in this model of hypertension.
本研究的目的是表征脑毛细血管内皮中的血管紧张素II（AII）受体，并研究在成年自发性高血压大鼠（SHR）的脑微血管中，AII反应性的第一步，即AII受体结合是否异常。利用[3H]血管紧张素II与来自Sprague-Dawley、Wistar-Kyoto和SHR大鼠的离体大脑皮质微血管的结合来表征这些血管上的AII受体。动力学实验得出的平衡衍生Kd（解离速率常数/结合速率常数）与从饱和结合数据的Scatchard分析获得的结果非常接近。数据表明，两种正常血压对照品系表现出相当的AII受体亲和力和结合能力。相比之下，对成年SHR微血管的实验表明，相对于对照，AII受体的Bmax显著更高。尽管评估SHR中AII功能性内皮改变的实验仍有待进行，但AII受体数量的增加表明血管AII反应性异常可能在该高血压模型中起重要作用。
