The Changing Pressor Response to Angiotensin II in Early Human Pregnancy

Abstract

Although it has been known for some years that the pressor response to angiotensin II (ANG II) is blunted in normotensive pregnancy, it is still not clear whether this is due to a form of specific competitive inhibition or to a more generalized change in the vasculature. Further to investigate this, formal studies of the ANG II dose: response curve have been carried out in pregnant and non-pregnant women. Thirty women (10 non-pregnant, 10 in first and 10 in second trimester pregnancy) have been studied. The pressor response to doubling doses of ANG II each maintained for 10 min. from just sub-pressor to that needed to evoke an increase in diastolic pressure of at least 20mmHg was studied. By a mean of 10 weeks gestation both the calculated diastolic threshold dose (PD₁) and that required to evoke a 20mmHg rise in pressure (PD₂₀) had increased significantly, and continued to do so in the second trimester (P<0.001 for both; ANOVA). The calculated slopes of the dose: response curyes were effectively identical (18.9±1.6 to 20.1±2.6mmHg/ngAII.kg min); the change was due to a progressive fall in intercept on the y axis. The systolic pressor response to ANG is less than the diastolic, but qualitatively similar changes were noted. There was no difference in the evoked bradycardia between pregnant and non-pregnant women.

The parallel shift in the dose: response curves strongly suggests a form of competitive inhibition. Since plasma ANG II concentrations are known to increase in early pregnancy it seems probable that the observed change in responsiveness at this time is directly related either to prior receptor occupancy or to down regulation of the ANG II receptor. Concentration-related stimulation of synthesis and/or release of a vasodilator eicosanoid(s) is another possibility.

Key Words:

• pregnancy
• renin-angiotensin system
• angiotensin II