A New Model to Evaluate the Hypertensive Response to Noxious Stimuli in the Anesthetized, Spontaneously Hypertensive Rat

We have developed a method to evaluate the hypertensive response after noxious stimuli in anesthetized rats. Anesthetic level, stimuli, and responses were standardized by using an etomidate infusion, a series of stimuli of increasing intensity applied to the tail, and measuring maximal changes in systolic blood pressure (ΔSBP) after each stimulus. Normotensive Sprague Dawley rats (SD) (n = 7) were studied using an etomidate infusion of 4.2 mg·kg−1·h−1. This method was then applied to spontaneously hypertensive rats (SHR) anesthetized with three rates of etomidate infusion: Group 1 (n = 8), 7.0 mg·kg−1·h−1; Group 2 (n = 8), 5.6 mg·kg−1·h−1; and Group 3 (n = 11), 4.2 mg·kg−1·h−1. Under anesthesia, three types of noxious stimuli were applied to the tail at 1-min intervals (13 total): (a) Type 1: 11 2-s electrical stimuli of increasing intensity (0.4–12 mA, to produce threshold to maximal responses); (b) Type 2: one intense, prolonged electrical stimulus (10 mA, 5 s); and (c) Type 3: tail-clamping. After each stimulus, ΔSBP was measured. In the SHR, comparing single ΔSBP responses to single noxious stimuli after each of the three most intense stimuli showed no statistically significant differences among the three anesthetic groups. In contrast, comparison of dose-response curves of multiple ΔSBP responses to multiple Type 1 (2-s) stimuli demonstrated a significant difference among the three anesthetic groups of SHR. Evaluating a series of hypertensive responses to a series of brief electrical stimuli of increasing intensity may allow greater discrimination of arterial blood pressure responses in different anesthetic groups of SHR, as compared to conventional methods of evaluating a single response to a single noxious stimulus. This may allow a different approach to study anesthesia in hypertensive subjects.