Potentiating Action of Desmethylimipramine on the Cardiovascular Effects of Noradrenaline and Some Other Pressor Agents

The influence of desmethylimipramine (DMI) on the cardiovascular responses to i.v. injected noradrenaline (NA), adrenaline, metaraminol and isoprenaline, as well as to some chemically unrelated pressor agents (angiotensin, vasopressin, and the vasopressin analogue felypressin), was studied in anesthetized dogs and cats. The cardiovascular effects of NA were potentiated very markedly by moderate doses of DMI (0.1–1.0 mg/kg). The responses to adrenaline and metaraminol were only slightly potentiated. In the case of adrenaline, DMI was slightly more effective in enhancing the pressor action of this amine after partial β-blockade (propranolol). In analogy with the carotid occlusion response, the effect on the peripheral vascular resistance elicited by electrical stimulation of the lumbar sympathetic nerves was not significantly potentiated by DMI. A method of “delayed autoperfusion” was developed to record reflex vasomotor counter-regulation. DMI was found to reduce the activity of this counter-regulation suggesting that this may be one way in which this drug potentiates the cardiovascular effects of the non-catecholamine pressor agents.