Evidence of dysfunctional beta(2)-adrenoceptor signal system in pre-eclampsia

Objectives: To determine how beta(2)-adrenoceptor binding and function diff er 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 overnigh t rest. The two groups were matched for gestational age which was (mean (SD )) 36.4 (3.8) and 36.5 (4.4) weeks for the preeclamptic and control groups, respectively. Six weeks after delivery a second blood sample was obtained. The binding and function of beta(2)-adrenoceptors were determined in isola ted human mononuclear leukocytes. The levels of adrenaline and noradrenalin e were determined in plasma from venous blood. Results: An elevated density of functional beta(2)-adrenoceptors was observ ed in normal pregnancy [mean (SD) 390 (90) vs 270 (60) sites/cell postpartu m], due to an increased fraction of receptors in high affinity state, with unaltered total receptor density. The number of functional beta(2)-adrenoce ptors was reduced in pre-eclampsia [mean (SD) 80 (40) vs 240 (30) sites/cel l postpartum], due to a reduction in the total receptor number with an unal tered fraction of high affinity receptors. In pregnancy, both unstimulated and isoprenaline-stimulated cAMP levels were reduced in the women with pre- eclampsia (0.5 (0.2) and 1.7 (0.9) pmol/10(6) cells, respectively) compared with the normal pregnant controls (mean (SD) 1.2 (0.3) and 4.7 (1.8) pmol/ 10(6) cells, respectively). Plasma catecholamine levels were not elevated i n the women with pre-eclampsia. Conclusions: The increased number of functional beta(2)-adrenoceptors may c ontribute 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.