Altered number of platelet angiotensin II receptors in relation to plasma agonist concentrations in normal and hypertensive pregnancy

Abstract

Objective: The relation between plasma angiotensin II concentrations and the platelet angiotensin II receptor was examined in four different groups of subjects. Platelet receptors were used as representative of physiologically significant sites such as in vascular smooth muscle.

Subjects: A control group consisting of non-pregnant females was studied together with three pregnant groups: normal pregnant women in both early and then late gestation and women with diagnosed pregnancy-induced hypertension (PIH).

Methods: Blood was collected from each subject for estimation of plasma angiotensin II concentration and isolation of platelets, which were then used in non-competitive binding studies. Both receptor capacity and affinity for the ligand were calculated for each subject.

Results: In the control group, a significant negative correlation between angiotensin II and receptor capacity was established. This was in marked contrast to the first trimester group which showed no such correlation and where there was a significant reduction or nil receptor capacity but only a slight elevation in mean plasma angiotensin II concentration. This phenomenon of reduced or absent binding persisted into the third trimester when plasma angiotensin II was significantly elevated compared with all other groups. PIH subjects had the lowest plasma angiotensin levels and 90% had clearly measurable binding to the platelet receptor, which was not however as high as that in the control group. Two normotensive subjects who demonstrated significant potentiation of receptor binding in the third trimester subsequently developed PIH.

Conclusions: The inverse relation between plasma angiotensin II and its platelet receptor, found in non-pregnant subjects, is significantly altered in normal pregnancy. Reduced receptor capacity and lack of relation with circulating ligand observed in early gestation reflects an alteration at the receptor level which is independent of plasma angiotensin II concentration. This alteration appears to persist throughout pregnancy except in subjects predisposed to PIH when receptor binding is closer to non-pregnant values. Changes in receptor binding found in people who ultimately developed PIH but who were still clinically normal at the time suggest that binding to the platelet receptor could be used as a screening test for all primiparae to identify those predisposed to PIH later on in pregnancy.