The interaction between serotonin and angiotensin II in the chronically instrumented guinea pig and its alteration by indomethacin.

We examined the effect of a subthreshold infusion of serotonin on the angiotensin II pressor response in the chronically instrumented pregnant and nonpregnant guinea pig before and after administration of a prostaglandin synthesis inhibitor. Arterial blood pressure was significantly lower in the pregnant animal (p = 0.0135). An infusion of serotonin, which failed to alter the blood pressure, pulse, or uterine artery flow velocity, significantly increased the pressor response to angiotensin II infused at 3.5, 7.5, 14.5, and 29 ng/kg/min in both the pregnant (p = 0.0001) and, to a lesser degree, the nonpregnant animal (p = 0.004). Pretreatment with indomethacin heightened the angiotensin pressor effect significantly in the pregnant group (p = 0.0001) and to a near-significant degree in the nonpregnant group (p = 0.074). However, indomethacin enhanced the angiotensin II-serotonin synergism only in the pregnant animal (p = 0.0008). The angiotensin II-serotonin synergism persisted after pretreatment with the sympathetic blocking agent bretylium tosylate. We concluded that serotonin augments the pressor effect of angiotensin II in the pregnant and nonpregnant guinea pig; however, this synergism is potentiated by the inhibition of prostaglandin synthesis only in the pregnant animal.