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Significant modifications of the uterine circulation are observed during pregnancy, with uterine circulation accounting for up to 11% of cardiac output at the end of pregnancy. We studied the reactivity of the uterine microcirculation to determine the time course of uterine mechanical and pharmacological alterations during pregnancy and postpartum. Arcuate artery segments, obtained from virgin, pregnant (7, 14, and 22-23 days), and postpartum (5 days) rats, were set up in wire myographs for microvessels under a passive tension equivalent to a transmural pressure of 50 mmHg (L50). Cumulative concentration-response curves to angiotensin II (ANG II), phenylephrine (PE), and potassium chloride (KCl) were measured. Diameter of the arcuate artery at L50 increased progressively until term from 108 +/- 4 microns in virgins to 188 +/- 9 microns at day 22 of pregnancy. This increase in diameter was partially reversed at day 5 postpartum (151 +/- 9 microns). Surprisingly, the passive length-tension relationship on arcuate arteries showed greater stiffness from day 14 of pregnancy through day 5 postpartum. The maximum response of the arteries to ANG II was markedly increased during pregnancy (from 0.78 +/- 0.02 to 1.43 +/- 0.09 mN/mm at day 22) and was already evident at day 14 (1.20 +/- 0.07 mN/mm) but was reversed in postpartum rats (0.81 +/- 0.04 mN/mm, nonsignificant). Similar results were obtained for maximum responses to PE and KCl, but the reversal at day 5 postpartum was only partial. Sensitivity (measured as the negative log of the concentration of stimulant required to produce 50% of the maximum response) of the uterine arcuate artery to the three vasopressors increased during the postpartum period and also at day 21 of pregnancy with PE and day 14 with KCl. The present results show that the uterine arcuate artery doubles in diameter during pregnancy. This increase in diameter is accompanied by increased stiffness of the vessel and heightened responsiveness to ANG II, PE, and KCl. These data demonstrate that pregnancy induces changes in reactivity of the rat uterine arcuate artery that appear to be linked to modifications in the mechanical properties of the vessel, at least for ANG II and PE.

Pregnancy is associated with decreased vascular responsiveness to vasopressor stimuli. We have tested the involvement of Ca2+ mobilization in myotropic responses of aortic rings obtained from pregnant and virgin rats. Contractions of the rings to phenylephrine, in the absence of calcium in the bathing medium, were lower in tissues from virgin than from pregnant rats. Concentration-response curves to CaCl2 that were measured after stimulation by phenylephrine in the absence of Ca2+ were shifted to higher levels of contraction. This was not observed when KCl was used to prestimulate the aorta. D-600, a phenylalkylamine calcium channel blocker, similarly inhibited these responses to CaCl2 in tissues from both pregnant and virgin animals. D-600 exerted a concentration-dependent inhibition of responses to phenylephrine and KCl. However, the calcium antagonist was less effective in aortic rings of pregnant than of virgin rats. Basal 45Ca2+ uptake was lower in aortic rings from pregnant than from virgin rats, and Bay K 8644 was unable to reverse this difference. The time course of basal and stimulated (KCl) 45Ca2+ influx was lower in aorta of pregnant rats at all times studied. Moreover, when the intracellular calcium pools were emptied with phenylephrine, the refilling of these pools was delayed in aortic rings of pregnant rats. These results indicate an altered extracellular calcium mobilization of aortic rings from pregnant rats. These changes may be due to a functional alteration of the voltage-operated calcium channels during pregnancy.

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