Hypothesis: selective phosphodiesterase-5 inhibition improves outcome in preeclampsia

Downing, J.W.; Ramasubramanian, R.; Johnson, R. F.; Minzter, Beth H.; Paschall, Ray L.; Sundell, Håkan; Engelhardt, Barbara; Lewis, RM

doi:10.1016/j.mehy.2004.03.042

Cited by 36 publications

(26 citation statements)

References 39 publications

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“…It has also recently been hypothesized that selective PDE5 inhibition has a possible beneficial effect in the treatment of preeclampsia. 36 Immunocytochemical and Western blot experiments performed in the present study show that PDE5 is basally expressed in primary cultures of human myometrial cells. Moreover, PDE5 enzymatic activity is detectable in these culture systems.…”

Section: Discussionsupporting

confidence: 56%

Regulation of Phosphodiesterase 5 Expression and Activity in Human Pregnant and Non-pregnant Myometrial Cells by Human Chorionic Gonadotropin

Belmonte

Ticconi

Dolci³

et al. 2005

Journal of the Society for Gynecologic Investigation

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Section: Discussionsupporting

confidence: 56%

Regulation of Phosphodiesterase 5 Expression and Activity in Human Pregnant and Non-pregnant Myometrial Cells by Human Chorionic Gonadotropin

Belmonte

Ticconi

Dolci³

et al. 2005

Journal of the Society for Gynecologic Investigation

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“…Recent studies have demonstrated that sildenafil citrate significantly enhances vasodilation of myometrial small arteries and is also associated with fetal weight gain which offers a potential therapeutic possibility for IUGR [16].…”

Section: Discussionmentioning

confidence: 99%

The use of low dose sildenafil citrate in cases of intrauterine growth restriction

Mohammed¹,

Alashkar²,

Abdeldayem³

et al. 2017

Clin Obstet Gynecol Reprod Med

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Introduction: Intrauterine growth restriction [IUGR] is defined as a birth weight less than the 10th percentile for gestational age. It has a prevalence of the 5-8% in the general population. It represents the second cause of perinatal mortality, after prematurity. Sildenafil citrate is a phosphodiesterase5 (PDE-5) inhibitor, delaying the breakdown of cyclic guanosine monophosphate (cGMP) and enhancing nitric oxide (NO)-dependent vasodilatation. Sildenafil citrate is increasingly used for pulmonary hypertension in pregnancy, and is also emerging as a potential candidate for the treatment of intra-uterine growth retardation and for premature labour.

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“…In 2004, Downing et al (6) published the hypothesis that selective PDE5 inhibition may be an option for the treatment of preeclampsia. Sildenafil improves endothelial function of myometrial vessels ex vivo from women whose pregnancies are complicated by IUGR (21) and produces a cGMP-dependent vasodilation in second-order chorionic plate arteries obtained from patients after normal pregnancy (10).…”

Section: Discussionmentioning

confidence: 99%

“…It has been hypothesized that the phosphodiesterase-5 (PDE5) inhibitor sildenafil may be useful in the treatment of hypertension during pregnancy and IUGR (6,20). Sildenafil improves endothelial function of myometrial vessels ex vivo from women whose pregnancies are complicated by IUGR (21) and induces vasodilation of chorionic plate arteries from women with normal pregnancies (10).…”

mentioning

confidence: 99%

Effects of sildenafil on maternal hemodynamics and fetal growth in normal rat pregnancy

Sasser¹,

Baylis

2010

American Journal of Physiology-Regulatory, Integrative and Comp

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It has been suggested that the phosphodiesterase-5 (PDE5) inhibitor sildenafil may be useful in the treatment of hypertension during pregnancy. However, we have reported a selective increase in renal inner medullary PDE5 that participates in the sodium retention of pregnancy. Therefore, the purpose of this study was to determine whether oral sildenafil treatment impairs maternal plasma volume expansion and/or fetal growth during rat pregnancy. Rats received sildenafil (10 mg x kg(-1) x day(-1), 50 mg x kg(-1) x day(-1), or 90 mg x kg(-1) x day(-1)) or vehicle on days 4-20 of pregnancy. On days 14-19, rats were housed in metabolic cages for collection of urine and measurement of food and water intake. Terminal hemodynamic and fetal measurements were taken on day 20. None of the sildenafil doses lowered blood pressure, and although all doses increased plasma cGMP concentrations, only the highest dose increased aortic and inner medullary cGMP content. Sildenafil had no effect on maternal weight gain; however, the highest dose decreased both plasma volume and renal sodium retention. The pup number and size were similar among the groups. Therefore, these studies suggest that low doses of systemic sildenafil may be safe during pregnancy in the rat, but higher doses may interfere with the physiological sodium retention and volume expansion of pregnancy. The effects of systemic sildenafil on blood pressure and sodium retention during hypertension in human pregnancy remain to be examined.

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Hypothesis: selective phosphodiesterase-5 inhibition improves outcome in preeclampsia

Cited by 36 publications

References 39 publications

Regulation of Phosphodiesterase 5 Expression and Activity in Human Pregnant and Non-pregnant Myometrial Cells by Human Chorionic Gonadotropin

Regulation of Phosphodiesterase 5 Expression and Activity in Human Pregnant and Non-pregnant Myometrial Cells by Human Chorionic Gonadotropin

The use of low dose sildenafil citrate in cases of intrauterine growth restriction

Effects of sildenafil on maternal hemodynamics and fetal growth in normal rat pregnancy

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