The Interaction of Serotonin, Norepinephrine, Epinephrine, and Angiotensin II During Pregnancy

Abstract

Serotonin augments synergistically the pressor response of the guinea pig to angiotensin II. We hypothesized that serotonin would enhance the effects of other vasoactive agents and that these agents themselves would have synergistic properties similar to serotonin. We tested this hypothesis by administering to chronically instrumented pregnant guinea pigs a] norepinephrine and epinephrine with and without a concurrent continuous subthreshold infusion of serotonin; and b] angiotensin II with and without a concurrent continuous subthreshold infusion of epinephrine. The subthreshold infusions altered neither baseline MAP, heart rate, uterine blood flow velocity (UBFV) as measured by a miniaturized Doppler flow probe, nor the calculated uterine resistance (UR). Norepinephrine and epinephrine produced significant dose-dependent alterations in MAP, UBFV, and UR (all p < 0.001). Serotonin significantly enhanced the pressor response to both norepinephrine (p = 0.0006) and epinephrine (p = 0.03) while either ameliorating the catecholamine mediated decline in UBFV and increase in UR. The subthreshold infusion of epinephrine actually reduced the angiotensin II pressor response (p < 0.0001) while it significantly blunted the expected rise in UBFV (p < 0.0001) which occurs with these doses of angiotensin II. We conclude that the synergism by serotonin for the pressor effect of angiotensin II, norepinephrine, and epinephrine is not a property shared by epinephrine for angiotensin II. And while a subthreshold infusion of serotonin blunts the adverse effects of norepinephrine and epinephrine upon uterine blood flow, a subthreshold infusion of epinephrine blunts the increase in uterine blood flow normally associated with a low dose of angiotensin II. We speculate that the explanation for these apparent divergent responses involves differences in the affect of these agents upon endothelial activity.