Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.788518
Title: Immunological markers, antioxidants and prostaglandins in pregnancy-induced hypertension
Author: Chen, Gong
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1993
Availability of Full Text:
Access from EThOS:
Access from Institution:
Abstract:
Pregnancy-induced hypertension (PIH) is still a major cause of obstetrical and perinatal morbidity and mortality, and no breakthrough has yet been achieved in the understanding of its pathogenesis. The present in vitro work studied the pathogenesis of PIH in three aspects: immunology, antioxidants and prostaglandins using various immunological, biochemical and molecular genetic methods. An increased cellular immunological activity was detected in patients with PIH, especially in those with proteinuria, as the proliferation of peripheral blood mononuclear cells (PBMC) with PHA stimulation and without mitogens was increased and the IL-2 activity was elevated compared to normotensive pregnant women. The hypersecretion of IgG from B lymphocytes was also found in patients with PIH. The increased immunological activity is in accordance with some important changes seen in PIH, such as an increased intracellular calcium, the presence of a blood-borne mitogenic factor and a decreased prostaglandin E series. These findings support the hypothesis that PIH may result from the imbalance between fetal antigenic load and maternal production of immunological blockage. Intracellular (lysate thiol, lysate glutathione and lysate superoxide dismutase (SOD) in red blood cells) and extracellular (plasma thiol, plasma glutathione and red blood cell membrane thiol) antioxidant buffering levels were investigated in patients with PIH and both of them were decreased in the patients, suggesting an occurrence of increased reactive oxygen species (ROS) activity in this disorder. It was also found that there were significant positive correlations between the levels of prostaglandins and antioxidant activity. It was possible that the changes of prostaglandin production resulted from the imbalance of decreased antioxidant buffering levels and increased ROS formation in PIH. The cause of the decreased antioxidant levels in PIH is not clear. However the reduced SOD (CuZn) activity seems to be an acquired phenomenon since its gene structure and expression in PIH did not differ from that in normal subjects. Production of prostacyclin (PGI2) and thromboxane A2 (TXA2) in mononuclear cells was determined in patients with PIH and the effects of PIH serum on this production were investigated. The results showed that the imbalance of decreased PGI2 and increased TXA2 production occurred in mononuclear cells from PIH patients and thus the ratio of TXA2 to PGI2 was increased. Serum from PIH patients with proteinuria slightly reduced PGI2 synthesis in normal pregnant women but markedly increased TXA2 production, producing a ratio of TXA2 to PGI2 similar to that found in PIH. This result suggested that there was a factor(s) in serum from PIH patients with proteinuria to contribute, at least in part, to the imbalance between PGI2 and TXA2 seen in PIH. PIH and essential hypertension in pregnancy have an important clinical feature in common, high blood pressure, however, the cause of this remains unclear. The immunological markers and the antioxidant agents were evaluated in both diseases. The results showed that immunological changes found in PIH did not occur in essential hypertension in pregnancy. Antioxidant agents were decreased in both diseases, however the types of antioxidants involved were different. There results suggested that different pathogenetic mechanisms may associated with these two disorders. The effects of antihypertensive drugs (atenolol, labetalol, methyldopai nifedipine and nimodipine) on antioxidants were also studied and the results indicated that atenolol and labetalol in vitro possessed some antioxidant activity as they can significantly raise the levels of plasma thiol and membrane thiol. The other three drugs were not found to have any antioxidant property. Taken together, the work in this thesis suggests that the cause of PIH is complicated and multifactorial. The disorder occurred in the immune system might be an important factor in triggering the development of PIH. The immunological maladaptation could lead to the imbalance between antioxidant levels and ROS activity. The balance of PGI2 and TXA2 was shifted to the TXA2 dominance and this change could contribute to many if not all of the pathophysiological features found in PIH. The decreased antioxidants and increased ROS activity may damage enthothelial cells and cause an imbalance of PGI2 and TXA2 production, and thus it forms the link between the immune system and endothelial dysfunction.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.788518  DOI: Not available
Share: