Graduate Program in Neuroscience and Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, Minnesota; and.
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan.
Am J Physiol Heart Circ Physiol. 2014 Sep 1;307(5):H670-9. doi: 10.1152/ajpheart.00922.2013. Epub 2014 Jul 3.
Angiotensin II (ANG II)-induced hypertension is a commonly studied model of experimental hypertension, particularly in rodents, and is often generated by subcutaneous delivery of ANG II using Alzet osmotic minipumps chronically implanted under the skin. We have observed that, in a subset of animals subjected to this protocol, mean arterial pressure (MAP) begins to decline gradually starting the second week of ANG II infusion, resulting in a blunting of the slow pressor response and reduced final MAP. We hypothesized that this variability in the slow pressor response to ANG II was mainly due to factors unique to Alzet pumps. To test this, we compared the pressure profile and changes in plasma ANG II levels during subcutaneous ANG II administration (150 ng·kg(-1)·min(-1)) using either Alzet minipumps, iPrecio implantable pumps, or a Harvard external infusion pump. At the end of 14 days of ANG II, MAP was highest in the iPrecio group (156 ± 3 mmHg) followed by Harvard (140 ± 3 mmHg) and Alzet (122 ± 3 mmHg) groups. The rate of the slow pressor response, measured as daily increases in pressure averaged over days 2-14 of ANG II, was similar between iPrecio and Harvard groups (2.7 ± 0.4 and 2.2 ± 0.4 mmHg/day) but was significantly blunted in the Alzet group (0.4 ± 0.4 mmHg/day) due to a gradual decline in MAP in a subset of rats. We also found differences in the temporal profile of plasma ANG II between infusion groups. We conclude that the gradual decline in MAP observed in a subset of rats during ANG II infusion using Alzet pumps is mainly due to pump-dependent factors when applied in this particular context.
血管紧张素 II（ANG II）诱导的高血压是实验性高血压的常用模型，特别是在啮齿动物中，通常通过皮下给予 ANG II 使用 Alzet 渗透微型泵慢性植入皮下来产生。我们观察到，在接受这种方案的动物亚组中，平均动脉压（MAP）从 ANG II 输注的第二周开始逐渐开始下降，导致缓慢加压反应减弱和最终 MAP 降低。我们假设这种 ANG II 缓慢加压反应的可变性主要归因于 Alzet 泵特有的因素。为了验证这一点，我们比较了使用 Alzet 微型泵、iPrecio 植入式泵或 Harvard 外部输注泵皮下给予 ANG II（150ng·kg-1·min-1）时的压力曲线和血浆 ANG II 水平的变化。在 ANG II 治疗 14 天后，MAP 在 iPrecio 组最高（156 ± 3mmHg），其次是 Harvard 组（140 ± 3mmHg）和 Alzet 组（122 ± 3mmHg）。缓慢加压反应的速率，通过测量 ANG II 第 2-14 天期间每天压力的平均增加来表示，在 iPrecio 和 Harvard 组之间相似（2.7 ± 0.4 和 2.2 ± 0.4mmHg/天），但在 Alzet 组中明显减弱（0.4 ± 0.4mmHg/天），因为在一组大鼠中 MAP 逐渐下降。我们还发现了不同输注组之间血浆 ANG II 时间曲线的差异。我们得出结论，在使用 Alzet 泵输注 ANG II 期间，一组大鼠中观察到的 MAP 逐渐下降主要归因于在这种特定情况下应用时与泵相关的因素。
