title: Placental imbalance of vasoactive factors does not affect pregnancy outcome in patients treated with Cyclosporine A after transplantation.
abstract: Endothelin-1 (ET-1) and nitric oxide (NO) have been suggested to have a focal role in the regulation of placental and fetal growth. Cyclosporine A (CsA) has been shown to strongly modulate ET-1 and NO synthesis and thus has the potential to affect fetal growth and maternal state. Eleven CsA-treated female kidney transplant recipients were recruited. Fourteen healthy pregnant women served as controls. Placental expression of ET-1 and tissue factor (TF) was evaluated by in situ hybridization, and NO synthase (NOS) was evaluated by staining with the reduced form of nicotinamide-adenine dinucleotide phosphate (NADPH)-diaphorase and in situ hybridization. Kidney transplant recipients showed a marked reduction in NADPH-diaphorase staining, as well as endothelial constitutive NOS (ecNOS) messenger RNA, whereas inducible NOS expression was unchanged. Normal placenta showed a strong positive ET-1 signal along the endothelium of uteroplacental arteries within the basal plate, which increased markedly in decidua of transplant recipients. Thus, transplant recipients showed a remarkable alteration in ET-1/ecNOS balance without alteration in fetal growth or maternal renal function. Next, we explored the state of placental endothelial cell activation downstream from vasoactive factors by evaluating TF gene expression. Transplant recipients did not show modification of TF transcript compared with healthy pregnant women. CsA potently affected the placental ET-1/ecNOS vasoactive balance. Nevertheless, newborns from transplant recipient mothers were appropriate for gestational age, and transplant recipients did not show systemic hypertension or impending renal damage. It is suggested that CsA may blunt the activation of endothelial cells and priming of endothelial-derived substances, which possibly lie downstream from the cited vasoactive agents.
authors.affiliation: Department of Emergency and Organ Transplant, Division of Nephrology, University of Bari, Policlinico, Baria, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Di Paolo
authors.forename: Raffaella
authors.initials: R
authors.lastname: Monno
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stallone
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Grandaliano
authors.forename: Antonio
authors.initials: A
authors.lastname: Schena
authors.forename: Pantaleo
authors.initials: P
authors.lastname: Greco
authors.forename: Paolo
authors.initials: P
authors.lastname: Volpe
authors.forename: Leonardo
authors.initials: L
authors.lastname: Resta
authors.forename: Luigi
authors.initials: L
authors.lastname: Selvaggi
authors.forename: F Paolo
authors.initials: FP
authors.lastname: Schena
authors.forename: Loreto
authors.initials: L
authors.lastname: Gesualdo
mesh_terms: D000328:Adult; D016572:Cyclosporine / Q000494:pharmacology*; D019332:Endothelin-1 / Q000378:metabolism*; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D016030:Kidney Transplantation / Q000502:physiology*; D009252:NADPH Dehydrogenase / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011256:Pregnancy Outcome; D013925:Thromboplastin / Q000378:metabolism
chemical_list: D019332:Endothelin-1; D016572:Cyclosporine; D013925:Thromboplastin; D019001:Nitric Oxide Synthase; D009252:NADPH Dehydrogenase