The Effect of Maternal Ketanserin Treatment on Foetal 5-HT Receptor Function in Umbilical Cord Artery of Pre-Eclamptic Patients

Abstract

Background: Maternal treatment with the 5-HT_2A receptor antagonist ketanserin (KT) in pre-eclamptic patients is associated with a high placental transmission of KT, resulting in pharmacologically active levels of KT in the umbilical cord artery (UCA) and the neonate. Prolonged exposure to a 5-HT receptor antagonist may influence the functionality of foetal 5-HT receptors and compromise foetal development. Objective: To study whether exposure to KT influences the characteristics of foetal 5-HT receptors, functional studies were performed on 5-HT_2A and 5-HT_1B/1D receptors in UCA from pre-eclamptic patients treated with KT. Methods: UCAs were obtained, immediately after delivery, from pre-eclamptic patients (n = 7), treated antenatally with intravenous KT. Pre-eclamptic patients (n = 13), not treated with KT (non-KT), were included as a control group. Segments of UCA were prepared and mounted in tissue baths and isometric force changes were determined. Cumulative concentration response curves to 5-HT and to the 5-HT_1B/1Dreceptor agonist sumatriptan were constructed in the absence or presence of the 5-HT_2A receptor antagonist KT or the 5-HT_1B/1D receptor antagonist GR125743, respectively. Results: All UCA segments showed contractile responses to both 5-HT and sumatriptan, and the concentration response curves showed a rightward shift with increasing concentrations of KT and GR125743, respectively, indicating the presence of functional 5-HT_2A and 5-HT_1B/1D receptors in the foetal tissue. No significant differences were found in maximum response (E_max)(expressed in percent of response on 100 mM KCl) or potency (pEC₅₀) of 5-HT in both groups (E_max = 141 ± 7.7%, pEC₅₀ = 7.67 ± 0.26 in KT-treated group and E_max = 162 ± 12.6%, pEC₅₀ = 7.69 ± 0.14 in non-KT treated group, respectively). No significant differences were found in the potency of the antagonist KT in both study groups (pK_b = 7.65 ± 0.31 in KT group and 7.46 ± 0.17 in non-KT group, respectively). Similarly, with sumatriptan, no significant differences were found between KT-treated patients and non-KT treated patients (E_max = 142 ± 16.2 and 140 ± 14.7%, respectively, pEC₅₀ = 6.17 ± 0.37 and 6.41 ± 0.28 respectively, pK_b of GR125743 = 7.83 ± 0.48 and 8.43 ± 0.29, respectively). Conclusion: Foetal exposure to KT in pre-eclamptic patients does not seem to influence the functional characteristics of 5-HT_2A and 5-HT_1B/1D receptors in the UCA.