一种用于评估清醒束缚正常血压大鼠药物诱发体位性低血压的模型。

A model for evaluation of postural hypotension induced by drugs in conscious restrained normotensive rats.

作者信息

Lee C H, Strosberg A M, Roszkowski A P, Warren L A

出版信息

J Pharmacol Methods. 1982 Jan;7(1):15-24. doi: 10.1016/0160-5402(82)90054-7.

Abstract

A rat model was developed for use in evaluating postural hypotensive activity of a compound. Conscious normotensive rats were restrained on a tilt board with special restrainers to avoid blocking limb circulation. Dose response curves were explored to delineate the potential postural hypotensive activity of a compound. In response to a 2-min 90 degree head-up tilt, only a negligible changes in blood pressure was observed in the control state. The conscious rat was therefore able instantaneously to compensate for postural change. This ability, however, was blocked by guanethidine. The compound induced a dose-related hypotension and a further, dose-dependent drop in blood pressure on tilt. Hydralazine, on the other hand, induced only dose-dependent hypotension, but no change in blood pressure response from control tilts. Since these findings appear to be in accord with human clinical data, this rat model may be suitable for use in evaluating potential postural hypotensive activity of compounds.

摘要

开发了一种大鼠模型，用于评估化合物的体位性低血压活性。使用特殊的固定装置将清醒的正常血压大鼠固定在倾斜板上，以避免阻碍肢体循环。探索剂量反应曲线以描绘化合物潜在的体位性低血压活性。响应2分钟90度头高位倾斜，在对照状态下仅观察到血压有微不足道的变化。因此，清醒大鼠能够即时补偿体位变化。然而，这种能力被胍乙啶阻断。该化合物引起剂量相关的低血压，并且在倾斜时血压进一步呈剂量依赖性下降。另一方面，肼屈嗪仅引起剂量依赖性低血压，但与对照倾斜时的血压反应相比无变化。由于这些发现似乎与人类临床数据一致，这种大鼠模型可能适用于评估化合物潜在的体位性低血压活性。