Inverse relationship between fenfluramine-induced prolactin release and blood pressure in humans

Although substantial evidence from experimental animals suggests that augme ntation and reduction in serotonergic neurotransmission both affect arteria l blood pressure (BP), it is unknown whether "tonic" central serotonergic a ctivity is related to resting BP variability in humans. We tested this hypo thesis in a community sample by evaluating the relationship between resting BP and a neuropharmacologic index of brain serotonergic activity (the fenf luramine challenge test). Subjects were 270 generally healthy men and women aged 25 to 60 years who were not receiving prescribed antihypertensive or psychotropic medications. The sample included 216 non-Hispanic whites and 4 7 blacks. Resting systolic BP ranged from 85 to 161 mm Hg and diastolic fro m 58 to 98 mm Hg. Each subject received 0.55 to 0.65 mg/kg D,L-fenfluramine hydrochloride, and the plasma prolactin concentration was measured over 3. 5 hours. Analyses revealed a linear, inverse relationship between the maxim um fenfluramine-induced prolactin rise and systolic and diastolic BP in whi tes: r=-0.36 and r=-0.29, respectively (P<0.001 for both). These relationsh ips were not observed in the black participants. In whites, the prolactin r esponse to fenfluramine remained a significant predictor of systolic and di astolic BPs in multivariate models including age, gender, body mass index, physical activity, smoking, and alcohol consumption (P less than or equal t o 0.001). When compared with subjects in the highest quartile of prolactin response, individuals whose prolactin responses to fenfluramine comprised t he lowest quartile were 2.6 times more likely to have a resting systolic/di astolic BP of >135/85 mm Hg. These data reveal that in white but not black adults, fenfluramine-induced prolactin release correlates inversely with BP and may indicate a role of central serotonergic activity in the pathogenes is of hypertension.