Alterations of placental vascular function in asthmatic pregnancies.

Asthma during pregnancy is associated with low-birthweight neonates at term but the mechanisms that cause this outcome are presently unknown. Changes in placental vascular function resulting from asthma or its treatment could contribute to altered fetal growth. We have prospectively followed women with asthma and a control group of women without asthma during their pregnancies, classified them based on asthma severity and glucocorticoid intake, and monitored fetal development and placental blood flow using Doppler ultrasound at 18 and 30 wk gestation. The placentae from these women were collected after delivery and vascular responses to dilator and constrictor agonists assessed using an in vitro placental perfusion method. At 18 wk gestation, umbilical artery flow velocity waveforms were significantly reduced in the moderate and severe asthmatic groups and in those women using high-dose inhaled glucocorticoid for the treatment of their asthma (ANOVA, p < 0.05). However, at 30 wk gestation there were no significant differences in umbilical artery flow velocity between control and asthmatic women (ANOVA, p > 0.05). Corticotropin-releasing hormone (CRH), a potent vasodilator that acts via the nitric oxide pathway, caused a dose-dependent vasodilatory response in all placentae in vitro. However, CRH-induced dilation was significantly reduced in moderate and severe asthmatics (ANOVA, p < 0.05). Vasoconstrictor responses to potassium chloride and prostaglandin F(2alpha) were reduced in placentae from moderate and severe asthmatic women (ANOVA, p < 0.05). These studies demonstrate significant differences in placental vascular function in pregnancies complicated by asthma, which may relate directly to the asthma or be a consequence of the associated glucocorticoid treatment. These changes in vascular function in asthmatic pregnancies may contribute to the low-birthweight outcome observed in this condition.

Vasoactive effects of 8-epi-prostaglandin F(2alpha)in isolated human placental conduit and resistance blood vessels in vitro.

The effects of 8-epi-prostaglandin F(2alpha)(8-epi-PGF(2alpha)) and the thromboxane A(2)-mimetic U46619 were examined on isolated human fetal placental arteries obtained from normal pregnancies and from those complicated by pre-eclampsia. The effects of these agents were examined on both conduit and resistance arteries. 8-epi-PGF(2alpha)was found to be markedly less potent than U46619 in constricting both size vessels. Vasoconstrictor EC(50)s for 8-epi PGF(2alpha)were 4.10x10(-7) m (2.02-8.35x10(-7) m) (mean, 95 per cent CI and 2.05x10(-6) m (0.43-9.89 x10(-6) m) in conduit and resistance arteries, respectively. The maximum vasoconstriction produced by 8-epi-PGF(2alpha)(112+/-17 per cent), (relative to maximum KCl induced vasoconstriction) in conduit vessels was significantly less than that caused by U46619 (152+/-20 per cent). In resistance vessels the maximum vasoconstrictor effects to 8-epi-PGF(2alpha)(208+/-10 per cent) and U46619 (201+/-19 per cent) were similar, and in both cases significantly greater than the maximal effects seen in conduit vessels. U46619 displayed a similar vasoconstrictor potency in both conduit (EC(50)=1.21x10(-9) m, 0.58-2.51x10(-9) m) and resistance arteries [EC(50)=5.95x10(-9) m, (0.81-43.60x10(-9) m] as was found for 8-epi PGF(2alpha). 8-epi-PGF(2alpha)was equipotent in resistance arteries obtained from women with severely pre-eclamptic pregnancies (EC(50)=1.25x10(-6) m, 0.25-6.17x10(-6) m) compared with normotensive controls. However, the maximum vasoconstrictor effect induced by 8-epi-PGF(2alpha)in placental resistance arteries was significantly reduced (99+/-20 per cent) in vessels obtained from severely pre-eclamptic compared with normal pregnancies. These results indicate that 8-epi-PGF(2alpha)displays differential vasoconstrictor activity in the fetal-placental vasculature. Furthermore the vasoconstrictor effects of 8-epi-PGF(2alpha)are reduced in pre-eclampsia, the effect being selective to placental resistance vessels. This reduction may occur as a result of more serious disturbances in the placental microcirculation with the disease process in pre-eclampsia.