Evidence of dysfunctional beta2-adrenoceptor signal system in pre-eclampsia.

摘要

OBJECTIVES: To determine how beta2-adrenoceptor binding and function differ between healthy women and those with pre-eclampsia. DESIGN: Case-control study. SETTING: Faculty of Medicine, University of Tromso, Norway. PARTICIPANTS: Two groups of pregnant women: eight cases with pre-eclampsia, matched with eight healthy controls. METHODS: Venous blood was drawn from women in both groups after an overnight rest. The two groups were matched for gestational age which was (mean (SD)) 36 x 4 (3 x 8) and 36 x 5 (4 x 4) weeks for the pre-eclamptic and control groups, respectively. Six weeks after delivery a second blood sample was obtained. The binding and function of beta2-adrenoceptors were determined in isolated human mononuclear leukocytes. The levels of adrenaline and noradrenaline were determined in plasma from venous blood. RESULTS: An elevated density of functional beta2-adrenoceptors was observed in normal pregnancy [mean (SD) 390 (90) vs 270 (60) sites/cell postpartum], due to an increased fraction of receptors in high affinity state, with unaltered total receptor density. The number of functional beta2-adrenoceptors was reduced in pre-eclampsia [mean (SD) 80 (40) vs 240 (30) sites/cell postpartum], due to a reduction in the total receptor number with an unaltered fraction of high affinity receptors. In pregnancy, both unstimulated and isoprenaline-stimulated cAMP levels were reduced in the women with pre-eclampsia (0 x 5 (0 x 2) and 1 x 7 (0 x 9) pmol/10(6) cells, respectively) compared with the normal pregnant controls (mean (SD) 1 x 2 (0 x 3) and 4 x 7 (1 x 8) pmol/10(6) cells, respectively). Plasma catecholamine levels were not elevated in the women with pre-eclampsia. CONCLUSIONS: The increased number of functional beta2-adrenoceptors may contribute to the vasodilatation seen in normal pregnancy, while the reduced overall number of receptors may be one of several factors that account for increased peripheral vascular resistance in pre-eclampsia.