This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Napolitano, M. Articles by Lanzone, A. Search for Related Content PubMed PubMed Citation Articles by Napolitano, M. Articles by Lanzone, A.

Expression and Relationship between Endothelin-1 Messenger Ribonucleic Acid (mRNA) and Inducible/Endothelial Nitric Oxide Synthase mRNA Isoforms from Normal and Preeclamptic Placentas

Department of Experimental Medicine and Pathology, Università La Sapienza (N.M., C.A., V.A., G.A.); Department of Obstetrics and Gynecology, Università Cattolica del Sacro Cuore (M.F., A.R.), 00168 Rome; OASI Institute for Research (L.A.), 94018 Troina; and Neuromed Institute (G.A.), 86071 Pozzilli, Italy

Address all correspondence and requests for reprints to: Antonio Lanzone, M.D., Department of Obstetrics and Gynecology, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy. E-mail: SARA.LANZONE{at}TIN.it

Preeclampsia is a mainly vascular disease of pregnancy, probably caused by an imbalance between vasodilator and vasoconstrictor agents that results in generalized vasospasm and poor perfusion in many organs. Among these factors, endothelin-1 (ET-1), a potent vasoconstrictor, is highly increased in preeclamptic women, while nitric oxide (NO), a vasodilator of human utero-placental arteries, is reduced in the same patients. The present study was designed to investigate the interactions between ET-1 and the NO system in the feto-placental unit; to this purpose we also examined the messenger ribonucleic acid (mRNA) expression of ET-1, inducible NO synthase (iNOS), and endothelial NOS (eNOS) in human cultured placental trophoblastic cells obtained from preeclamptic (PE) and normotensive (NT) pregnancies. We also studied whether exogenous ET-1 may affect the expression of iNOS and eNOS in human placental trophoblastic cells. Interestingly, by Northern blot analysis we observed an increased ET-1 mRNA expression level in PE trophoblastic cells compared to NT trophoblastic cells. Furthermore, exogenous ET-1 (10^-7 mol/L) was able to up-regulate its own mRNA expression in both NT and PE trophoblastic cells. iNOS and eNOS mRNA expression was then detected, by semiquantitative PCR, in both NT and PE trophoblastic cells. PE trophoblastic cells expressed lower iNOS mRNA levels compared with NT pregnancies. On the contrary, eNOS mRNA expression was higher in PE trophoblastic cells than in NT cells. Moreover, in the presence of ET-1 we observed a decrease in iNOS and an increase in eNOS mRNA expression levels in both NT and PE trophoblastic cells compared with the respective untreated cells.

In conclusion, we demonstrate that ET-1 expression is increased in PE cells, whereas iNOS, which represents the main source of NO synthesis, is decreased; conversely, eNOS expression is increased. Finally, ET-1 is able to influence its own as well as NOS isoform expression in normal and PE trophoblastic cultured cells. These findings suggest the existence of a functional relationships between ET(s) and NOS isoforms that could constitute the biological mechanism leading to the reduced placental blood flow and increased resistance to flow in the feto-maternal circulation, which are characteristic of the pathophysiology of preeclampsia.

This article has been cited by other articles:

				M. Rosiansky-Sultan, E. Klipper, K. Spanel-Borowski, and R. Meidan Inverse Relationship between Nitric Oxide Synthases and Endothelin-1 Synthesis in Bovine Corpus Luteum: Interactions at the Level of Luteal Endothelial Cell Endocrinology, November 1, 2006; 147(11): 5228 - 5235. [Abstract] [Full Text] [PDF]

				G. Fiore, P. Florio, L. Micheli, C. Nencini, M. Rossi, D. Cerretani, G. Ambrosini, G. Giorgi, and F. Petraglia Endothelin-1 Triggers Placental Oxidative Stress Pathways: Putative Role in Preeclampsia J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4205 - 4210. [Abstract] [Full Text] [PDF]

				E. Karteris, M. Vatish, E. W. Hillhouse, and D. K. Grammatopoulos Preeclampsia Is Associated with Impaired Regulation of the Placental Nitric Oxide-Cyclic Guanosine Monophosphate Pathway by Corticotropin-Releasing Hormone (CRH) and CRH-Related Peptides J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3680 - 3687. [Abstract] [Full Text] [PDF]

				T. Hakli, E.-L. Romppanen, M. Hiltunen, S. Helisalmi, K. Punnonen, and S. Heinonen Endothelial Nitric Oxide Synthase Polymorphism in Preeclampsia Reproductive Sciences, April 1, 2003; 10(3): 154 - 157. [Abstract] [PDF]

				F. M. Reis, D. D'Antona, and F. Petraglia Predictive Value of Hormone Measurements in Maternal and Fetal Complications of Pregnancy Endocr. Rev., April 1, 2002; 23(2): 230 - 257. [Abstract] [Full Text] [PDF]