Evidence that imipramine-induced postural hypotension may be centrally mediated

The acute effects of imipramine upon cardiovascular reflexes have been studied in normal volunteers. Respiratory sinus arryhthmia, blood pressure and heart rate responses to standing, heart rate response to Valsalva's manoeuvre and the heart rate and blood pressure responses to isometric exercise were measured before and after 100 mg and 40 mg imipramine orally on separate occasions. Neither dose had an appreciable effect upon respiratory sinus arrhythmia (RSA), heart rate response to Valsalva or the responses to isometric exercise. Imipramine caused dose-related rises in resting heart rate and blood pressure. In view of the unchanged RSA these cannot be attributed to vagal blockade and may reflect peripheral noradrenaline reuptake inhibition. Imipramine profoundly altered the heart rate response to standing in a dose-related manner. This suggests an impairment of the orthostatic reflex. The presence of normal responses to the Valsalva manoeuvre and isometric exercise suggests that peripheral mechanisms were intact, and it is therefore likely that impairment of the orthostatic reflex is due to the effect of imipramine upon central monoaminergic neurones normally involved in this response.