Progesterone upregulates GABAA receptor expression in the sympathetic center of rats with preeclampsia / 第二军医大学学报

ABSTRACT

Objective To observe the expression of GABAa receptor in rostral ventrolateral medulla (RVLM) of preeclampsia (PE) rats, so as to explore the role of GABAa receptor in the mechanisms by which progesterone improves cardiovascular dysfunction in PE rats. Methods Desoxycorticosterone acetate (DOCA) was intraperitoneally injected and 0. 9% normal saline (NS) replaced the normal drinking water in pregnant rats to establish rat PE model, and the models were verified by measuring the mean arterial pressure (MAP), heart rate (HR), renal sympathetic nerve activity (RSNA), and concentration of 24-h urine protein. And the modll rats were set as pregnant+DOCA+ saline (PDS) group. The other three groups included the nonpregnant rats (Con) group, nonpregnant rats receiving DOCA and saline (DS) group, and normal pregnant rats (NP) group. The PDS and NP groups were further divided into two subgroups according to different treatments progesterone (17- OHPC) or NS administration, and the four groups were designated as NP+17-OHPC, NP+Veh, PDS+17-OHPC and PDS+ Veh groups. After three days of 17-OHPC treatment, the levels of progesterone in serum and cerebrospinal fluid were examined by the enzyme-linked immunosorbent assay (ELISA). The MAP, HR, RSNA and the 24-h urine protein were measured. Western blotting analysis was used to detect the protein expressions of GABAa receptor, GABAB receptor, and the nuclear progesterone receptors (nPGRA and nPGRB). Results Compared with Con, DS and NP groups, the MAP, RSNA and 24-h urine protein were increased significantly in PDS group (P<0. 05). Compared with NP group, progesterone levels in the serum and cerebrospinal fluid were significantly decreased in PDS group (P<0. 05). Three days after administration of progesterone to rats in PDS group, the MAP, RSNA and24-h urine protein were significantly reduced (P<0. 05), while the levels of progesterone in the serum and cerebrospinat fluid were significantly increased (P<0. 05). It was found that the expression of the GABAa receptor in RVLM was significantly decreased in PDS group compared with NP group (P<0. 05), which was reversed after 3 days’ administration of progesterone (P<0. 05). Compared with NP group, the expression of nPGRB was significantly increased in RVLM of rats in PDS group (P<0. 05), whereas progesterone treatment for 3 days produced a significant decrease of nPGRB (P<0. 05). The expressions of GABAB receptor and nPGRA were not significantly different between PDS and NP groups. Conclusion The expression of GABAA receptor is decreased in the RVLM of PE rats, which can be reversed by progesterone administration.