Effects and mechanisms of action of sildenafil citrate in human chorionic arteries.
AuthorsMaharaj, Chrisen H
Higgins, Brendan D
Morrison, John J
Laffey, John G
AffiliationDepartment of Anaesthesia, University College Hospital, Galway, Ireland. email@example.com
Cyclic Nucleotide Phosphodiesterases, Type 5
MetadataShow full item record
CitationEffects and mechanisms of action of sildenafil citrate in human chorionic arteries. 2009, 7:34 Reprod. Biol. Endocrinol.
JournalReproductive biology and endocrinology : RB&E
AbstractOBJECTIVES: 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 feto-placental 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. Inhibition of NO production with L-NAME did not attenuate the vasodilator effects of sildenafil. In contrast, sildenafil citrate significantly enhanced the vasodilation produced by the NO donor sodium nitroprusside. CONCLUSION: Phosphodiesterase-5 is present in the feto-placental circulation. Sildenafil citrate vasodilates the feto-placental circulation via a cGMP dependent mechanism involving increased responsiveness to NO.
- The effect of sildenafil on the altered thoracic aorta smooth muscle responses in rat pre-eclampsia model.
- Authors: Turgut NH, Temiz TK, Bagcivan I, Turgut B, Gulturk S, Karadas B
- Issue date: 2008 Jul 28
- Sildenafil treatment in vivo stimulates Leydig cell steroidogenesis via the cAMP/cGMP signaling pathway.
- Authors: Andric SA, Janjic MM, Stojkov NJ, Kostic TS
- Issue date: 2010 Oct
- Phosphodiesterase 5 and effects of sildenafil on cerebral arteries of man and guinea pig.
- Authors: Kruuse C, Khurana TS, Rybalkin SD, Birk S, Engel U, Edvinsson L, Olesen J
- Issue date: 2005 Oct 3
- Sildenafil and T-1032, phosphodiesterase type 5 inhibitors, showed a different vasorelaxant property in the isolated rat aorta.
- Authors: Mochida H, Inoue H, Takagi M, Noto T, Yano K, Kikkawa K
- Issue date: 2002 Apr 5
- Sildenafil is a pulmonary vasodilator in awake lambs with acute pulmonary hypertension.
- Authors: Weimann J, Ullrich R, Hromi J, Fujino Y, Clark MW, Bloch KD, Zapol WM
- Issue date: 2000 Jun