Effects of tricyclic antidepressants on cardiovascular responses to norepinephrine and phenylephrine during pregnancy.
The effects of imipramine and amitriptyline on the responses of the uteroplacental vasculature to norepinephrine and phenylephrine were investigated in the pregnant ewe. Experiments were performed on conscious animals in which electromagnetic flow transducers were chronically implanted on the uterine arteries. Administered alone, the tricyclic antidepressants had no effect on mean arterial pressure (MAP) or estimated uteroplacental vascular conductance (UPVCe). Following intravenous infusion of either imipramine (1 mg. per kilogram) or amitriptyline (2.5 mg. per kilogram), the pressor response to norepinephrine (1 microgram per kilogram) and the duration of that response were significantly increased (p less than 0.05). In addition, both the duration of the norepinephrine-produced decrease in uteroplacental blood flow (UPBF) and the amplitude of the decrease in UPVCe were enhanced. In contrast, responses to phenylephrine (2.5 microgram per kilogram) were unaffected by prior administration of either imipramine or amitriptyline. Of additional interest were findings suggesting differential sensitivities to alpha-agonists of the uteroplacental compared with other vascular beds. These observations bring attention to the possibility of interactions between endogenous or exogenous norepinephrine and the tricyclic antidepressants and suggest that the possibly unique sensitivities of the uteroplacental bed should be considered when prescribing drugs during pregnancy.
D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D007099:Imipramine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology*; D010920:Placenta / Q000098:blood supply*; D011247:Pregnancy; D011270:Pregnancy, Animal; D012039:Regional Blood Flow / Q000187:drug effects; D012756:Sheep; D014599:Uterus / Q000098:blood supply*
D000929:Antidepressive Agents, Tricyclic; D000639:Amitriptyline; D010656:Phenylephrine; D007099:Imipramine; D009638:Norepinephrine