Vasoreactivity of Chorionic Plate Arteries in Response to Vasoconstrictors Produced by Preeclamptic Placentas

Abstract

Inadequate blood flow and increased vasoconstriction of the placenta contribute to pregnancy associated disorders such as preeclampsia (PE). Because placental vessels lack autonomic innervation, humoral effects of the placenta must play critical roles in regulation of fetal-placental vascular contractility. In this study, we examined the nature of humoral factors produced by PE trophoblasts on placental vessel contractility using an organ bath perfusion model. Vasomotor responses were studied in vitro using placental chorionic plate arteries. Vessel rings from third branch chorionic plate arteries were dissected from human placentas following normal or PE delivery. The arterial rings were equilibrated in Krebs Henseleit buffer and exposed to placental conditioned medium, which was prepared by culture of villous tissue from PE placentas. Receptor antagonists for angiotensin II (ANG II), thromboxane (TX), and endothelin (ET) were used to determine which humoral factor produced by placental tissue (trophoblasts) was more effective in promoting vasoconstriction. The role of angiotensin converting enzyme (ACE) and non-ACE ANG II generating enzymes in regulation of placental vasomotor tone were also investigated. A total of 80 arterial rings from 48 placentas were studied. Our results showed: 1) enhanced vasomotor tone in arteries from PE placentas compared to those from normal placentas; 2) PE-CM induced vaso-constrictive activity could be partially attenuated by receptor antagonists for TX, ANG II and ET, respectively; and 3) chymostatin (a chymase inhibitor) produced a stronger inhibitory effect than captopril (ACE inhibitor) on PE conditioned medium induced vasoconstriction. Our data demonstrate increased vasocontractility in PE placentas and suggest that the non-ACE pathway is probably a major source of ANG II produced in the human placenta.

Contractility of Placental Vascular Smooth Muscle Cells in Response to Stimuli Produced by the Placenta: Roles of ACE vs. Non-ACE and AT1 vs. AT2 in Placental Vessel Cells

“…Our results showed that placental products could induce placental vessel cell contraction. This finding agrees with our previously published work using an organ bath perfusion model to study placental chorionic plate artery contractility [9]. We found that the ACE inhibitor captopril had little effects on placental VSMC contraction.…”

“…In the present study using the collagen gel contraction model, we used captopril and chymostatin to differentiate possible ACE from non-ACE Ang II generation induced placental VSMC contractility. We observed that captopril had no effect on VSMC contraction, but it could attenuate chorionic plate artery contractility observed in our previous organ bath perfusion study, in which placental chorionic plate vessel rings were used [9]. This discrepancy in response to captopril could be due to an intact vessel with endothelium contact [9] versus no endothelial interaction in cultured VSMCs in the present collagen gel contraction study.…”

“…We observed that captopril had no effect on VSMC contraction, but it could attenuate chorionic plate artery contractility observed in our previous organ bath perfusion study, in which placental chorionic plate vessel rings were used [9]. This discrepancy in response to captopril could be due to an intact vessel with endothelium contact [9] versus no endothelial interaction in cultured VSMCs in the present collagen gel contraction study. On the other hand, chymostatin, a specific chymase inhibitor, produced dose dependent inhibitory effects on placental vessel cell contraction.…”

“…Preeclampsia is defined severe if one or more of the following criteria is present: maternal blood pressure ≥160/110 mmHg; proteinuria >3+ or >5 g/24 h; oliguria of less than 500 ml in 24 h; intrauterine growth restriction, and presence of persistent headache or visual disturbances. Preeclamptic placental conditioned medium was prepared as previously described [9,15,16]. Briefly, villous tissue, excluding basal plates and fetal membranes, was incubated with serum free Dulbecco's Modified Eagles Medium (DMEM, Sigma Chemical Inc., St Louis, MO) for 48 h. At the end of incubation, the culture medium was collected and stored at -70 °C until use.…”

“…Using an organ bath perfusion model, we recently demonstrated that vasoconstrictors produced by preeclamptic placentas could induce constriction of chorionic plate arteries [9]. We further noticed that chymostatin, a specific inhibitor of chymase (chymotrypsin-like protease), exerted a stronger inhibitory effect than captopril, a specific inhibitor of angiotensin converting enzyme (ACE), in attenuating increased vasoactivity of the chorionic plate artery rings induced by stimuli in the preeclamptic placental conditioned medium [9].…”