Effects and mechanisms of action of sildenafil citrate in human chorionic arteries
- PDF / 1,205,284 Bytes
- 10 Pages / 610 x 792 pts Page_size
- 72 Downloads / 169 Views
BioMed Central
Open Access
Research
Effects and mechanisms of action of sildenafil citrate in human chorionic arteries Chrisen H Maharaj1,2, Daniel O'Toole1,2, Tadhg Lynch1,2, John Carney1,2, James Jarman1,2, Brendan D Higgins1,2, John J Morrison3 and John G Laffey*1,2 Address: 1Department of Anaesthesia, University College Hospital, Galway, Ireland, 2Department of Anaesthesia, Clinical Sciences Institute and National Centre for Biomedical Engineering Sciences, National University of Ireland, Galway, Ireland and 3Department of Obstetrics and Gynaecology, Clinical Sciences Institute, National University of Ireland, Galway, Ireland Email: Chrisen H Maharaj - [email protected]; Daniel O'Toole - [email protected]; Tadhg Lynch - [email protected]; John Carney - [email protected]; James Jarman - [email protected]; Brendan D Higgins - [email protected]; John J Morrison - [email protected]; John G Laffey* - [email protected] * Corresponding author
Published: 23 April 2009 Reproductive Biology and Endocrinology 2009, 7:34
doi:10.1186/1477-7827-7-34
Received: 6 November 2008 Accepted: 23 April 2009
This article is available from: http://www.rbej.com/content/7/1/34 © 2009 Maharaj et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Objectives: Sildenafil citrate, a specific phosphodiesterase-5 inhibitor, is increasingly used for pulmonary hypertension in pregnancy. Sildenafil is also emerging as a potential candidate for the treatment of intra-uterine growth retardation and for premature labor. Its effects in the fetoplacental circulation are not known. Our objectives were to determine whether phosphodiesterase-5 is present in the human feto-placental circulation, and to characterize the effects and mechanisms of action of sildenafil citrate in this circulation. Study Design: Ex vivo human chorionic plate arterial rings were used in all experiments. The presence of phosphodiesterase-5 in the feto-placental circulation was determined by western blotting and immunohistochemical staining. In a subsequent series of pharmacologic studies, the effects of sildenafil citrate in pre-constricted chorionic plate arterial rings were determined. Additional studies examined the role of cGMP and nitric oxide in mediating the effects of sildenafil. Results: Phosphodiesterase-5 mRNA and protein was demonstrated in human chorionic plate arteries. Immunohistochemistry demonstrated phosphodiesterase-5 within the arterial muscle layer. Sildenafil citrate produced dose dependent vasodilatation at concentrations at and greater than 10 nM. Both the direct cGMP inhibitor methylene blue and the cGMP-dependent protein kinase inhibitor Rp-8-Br-PET-cGMPS significantly attenuated the vasodilation produced by sildenafil citrate. Inhibiti
Data Loading...
