Prostacyclin Deficiency and Reduced Fetoplacental Blood Flow in Pregnancy-Induced Hypertension and Preeclampsia

Abstract

Background: Low endothelial generation of prostacyclin (PGI₂) is a typical feature of pregnancy-induced hypertensive disorders. The aim of the current study was to establish whether changes in PGI₂ are accompanied by alterations in fetoplacental blood flow and to test the hypothesis that PGI₂ deficiency contributes to reduced fetoplacental perfusion in pregnancy-induced hypertension (PIH) and preeclampsia. Methods: The study included 11 women with normal pregnancies, 12 with PIH/preeclampsia, and 7 with otherwise complicated pregnancies. Fetoplacental blood flow was assessed both by umbilical artery Doppler sonography measuring the resistance index (RI) and by means of neonatal birth weight. PGI₂ formation was measured in umbilical arteries prepared immediately after birth. PGI₂, RI and birth weight were correlated with and without correction for gestational age. Furthermore, data from patients with PIH/preeclampsia were compared with normal pregnancies as controls. Results: A significant inverse correlation was found between umbilical PGI₂ formation and umbilical RI and between birth weight and RI, whereas PGI₂ and birht weight were directly related. Patients with PIH/preeclampsia showed reduced PGI₂ formation, markedly increased gestational age-corrected RI and significantly reduced percentile birth weight. Conclusions: These results provide evidence showing that PGI₂ is a relevant mediator of fetoplacental blood flow and suggest an important role of PGI₂ deficiency in PIH/preeclampsia.

Hypothesis: Pentoxifylline explores new horizons in treatment of preeclampsia

“…Th-1 mediated immune responses impair trophoblastic invasion, placentation and placental circulation [30,[41][42][43][44][45][46] and these series of events result in endothelial dysfunction and increased vascular resistance [47][48][49][50][51]. As endothelial function deteriorates and vascular resistance increases, placental perfusion becomes worse and more impaired [52].…”

“…In preeclamptic patients, the balance between ROS/RNS is impaired, formation of NO and Prostacyclins are decreased within the endothelium, and the balance between Prostacyclin and Thromboxane is disturbed, the release of vasoconstrictive endothelin is enhanced, and sensitivity of vascular smooth muscle cells to vasoconstrictive agents (e.g., angiotensin II) is increased [47][48][49][50][51][52][53][54]. Endothelial dysfunction and impairment of angiogenesis/angiore generation under influence of sFlt-1 and sEndoglin, result in hypertension, glomerular injury, edema and proteinuria [47][48][49][50][51].…”

“…Endothelial dysfunction and impairment of angiogenesis/angiore generation under influence of sFlt-1 and sEndoglin, result in hypertension, glomerular injury, edema and proteinuria [47][48][49][50][51]. As albumin is secreted in urine, the hypo-albuminemia and further peripheral edema ensue.…”

“…In addition, Prostacyclins are produced to a lesser extent and balance between Prostacyclins and Thromboxanes is significantly disturbed. All these alterations increase coagulability and accelerate thrombus formation [47][48][49]. Under these circumstances, massive activation of thrombocytes will damage the erythrocytes and hemolysis ensues.…”

“…Hypertension, glomerular injury, edema and proteinuria are some other complications of preeclampsia [47][48][49][50][51]. Regardless of the major cause of proteinuria, filtration and subsequent re-absorption of inflammatory cytokines make tubular cells release further inflammatory cytokines (e.g., TNF-a, IL-1b and MCP-1), recruiting monocytes to interstitium, which leads to progressive interstitial nephritis [90,91].…”