Vascular responsiveness to pressor agents during human pregnancy

Several important conclusions from these investigations of pressor response to angiotensin II are worth reemphasizing. The normal pregnant woman develops vascular refractoriness to the pressor effects of angiotensin II (and other vasoactive agents. This vascular refractoriness is principally the consequence of decreased vasular smooth muscle responsiveness to angiotensin II rather than the consequence of altered blood volume or angiotensin II plasma concentration. These pregnancy-induced changes in vascular responsiveness to antigotensin II are in contrast to the nonpregnant subject, whose plasma concentrations of renin and/or angiotensin II are inversely proportional to vascular reactivity to angiotensin II. The mechanism that controls vascular refractoriness during normal pregnancy probably involves a localized prostaglandin action mediated through cycle nucleotides. The action of progesterone or one of its metabolites probably mediates the synthesis or the catabolism of locally produced prostaglandins or prostaglandin-like agents; however, a direct effect of progestins on vascular smooth muscle cannot be excluded at present. Disturbances in any of these components of the mechanism could lead to the loss of refractoriness to angiotensin II. Women who develop PIH begin losing angiotensin II refractoriness as early as 18 weeks before hypertension develops. The identification of this pathophysiologic process between the 28th and 32nd weeks of pregnancy provides the potential to predict the likelihood that hypertension will ensue. From an awareness of the prolonged, preclinical events that lead to PIH, it is evident that once hypertension is detected, the disease is already advanced, at least in a temporal sense. Indeed, even though pregnancy-induced hypertension often regresses in response to bed rest, the increased sensitivity to angiotensin that these women exhibit does not change during this decline in blood pressure, and impaired uteroplacental blood flow, as reflected by the placental clearance of dehydroisoandrosterone sulfate through estradiol, does not improve.