Pregnancy-induced hypertension in a rat heterogeneity model.

This thesis presents an approach to develop pregnancy-induced hypertension (PIH) in animals by means of an immunologic model. Hypertensive pregnancy disorders in man may be considered a clinical expression of maladaptation in pregnancy. Maladaptation disease develops early in pregnancy, a long time before the onset of clinical signs. There is evidence that maladaptation of the maternal immune system to the fetal allograft is involved in the etiology of PIH. Increased fetomaternal MHC-antigen compatibility and non-MHC-antigen incompatibility may be responsible for such maladaptation, and may therefore lead to the disease. Fetomaternal maladaptation is possibly responsible for the inadequacy, or even absence, early in pregnancy of trophoblast invasion in the walls of the spiral arteries. Later in pregnancy it may be responsible for the increased platelet activation, which is even observed in mild cases of PIH, by formation of immune complexes. This may lead to a disturbed prostacyclin/thromboxane balance, which appears to be an important mechanism in the development of clinical signs of PIH. The elevated thromboxane activity in patients with PIH, resulting from enhanced platelet activity, leads to local vasospasm and increased platelet aggregation. This may impair uteroplacental blood flow, in particular in case of insufficient trophoblast migration, which may lead to endothelial damage and a further decrease in prostacyclin production. There may also be a direct effect of immune complexes on the production of prostacyclin by placental endothelial cells. The pathophysiologic pathway, that leads from maladaptation to a disturbed prostacyclin/thromboxane balance, and finally to the clinical manifestations of PIH, is far from clear. To elucidate this problem animal experiments may be helpful. In this thesis the influence of parenteral heterogeneity was investigated with regard to signs of PIH, and of fetoplacental ischemia. In all pregnant Wistar rats near term lower systolic blood pressures and higher in vitro uterine artery 6-keto-PGFla production were found as compared with nonpregnant Wistar rats. After crossbreeding with Brown Norway males, however, the reduction in systolic blood pressure and the increase in 6-keto-PGFla production in these animals appeared to be less than in noncrossbred Wistar females.

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