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

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.