Maternal medicine: Increased serum phosphodiesterase activity in women with pre‐eclampsia

Costa, Bartira Ercí­lia Pinheiro da; Scocco, Caio Augusto; Poli-de-Figueiredo, Carlos Eduardo; Guimarães, JA

doi:10.1111/j.1471-0528.2006.00916.x

Cited by 18 publications

(10 citation statements)

References 12 publications

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“…23 Theoretically, pharmacological manipulation of vascular endothelial function could improve fetal oxygenation and hence fetal well-being in growth-restricted fetuses. 24 Recently, phosphodiesterase activity was shown to be enhanced in women with preeclampsia, 25 with studies suggesting that inhibition of phosphodiesterase may enhance nitric oxidemediated smooth muscle relaxation. 26 Sildenafil citrate improves endothelial function of myometrial vessels and enhances vasodilation of small arteries in women with a pregnancy complicated by IUGR 27 and causes relaxation of myometrium in women undergoing elective cesarean delivery.…”

Section: Discussionmentioning

confidence: 99%

Effects of Sildenafil in Nω-Nitro-l-Arginine Methyl Ester-Induced Intrauterine Growth Restriction in a Rat Model

et al. 2012

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Section: Discussionmentioning

confidence: 99%

Effects of Sildenafil in Nω-Nitro-l-Arginine Methyl Ester-Induced Intrauterine Growth Restriction in a Rat Model

et al. 2012

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“…Waldkirch et al (2005), working with human cavernous arteries contracted by norepinephrine, implicated PDE5 in the regulation of the vasodilatation associated to cGMP (Waldkirch et al, 2005). Some authors proposed the use of nitrovasodilators or PDE5 inhibitors for pregnant women with vascular complications (Amit et al, 1998;Downing et al, 2004;Pinheiro da Costa et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…The involvement of PDE3 and PDE5 in the modulation of cGMP-dependent relaxation was also observed in human pulmonary artery (Rabe et al, 1994). Due to the cGMP effects in fetoplacental circulation, some authors proposed the use of nitrovasodilators or PDE5 inhibitors for pregnant women with vascular complications (Amit et al, 1998;Downing et al, 2004;Pinheiro da Costa et al, 2006). Furthermore, nitric oxide (NO) and sodium nitroprusside (NO donor) were shown to induce relaxation of the human umbilical artery (Lovren and Triggle, 2000).…”

Section: Introductionmentioning

confidence: 99%

PDE4 and PDE5 regulate cyclic nucleotides relaxing effects in human umbilical arteries

Santos-Silva

Cairrão

Morgado

et al. 2008

European Journal of Pharmacology

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Cyclic nucleotides (cAMP and cGMP) are the main second messengers linked to vasodilatation. They are synthesized by cyclases and degraded by different types of phosphodiesterases (PDE). The effect of PDE inhibition and cyclases stimulation on 5-hydroxytryptamine (5-HT; 1 microM) and histamine (10 microM) contracted arteries was analysed. Stimulation of guanylate cyclase or adenylate cyclase relaxed the histamine- and 5-HT-induced contractions indicating that intracellular increase of cyclic nucleotides leads to vasodilatation of the human umbilical artery. We investigated the role of different PDE families in the regulation of this effect. The presence of the different PDE types in human umbilical artery smooth muscle was analysed by RT-PCR and the expression of PDE1B, PDE3A, PDE3B, PDE4C, PDE4D and PDE5A was detected. The unspecific PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX; 50 microM) relaxed histamine-contracted human umbilical artery on 47.4+/-7.2%. This effect seems to be due to PDE4 and PDE5 inhibition because among the selective PDE inhibitors used only the PDE4 inhibitor (rolipram; 1 microM) and the PDE5 inhibitors (dipyridamole and T0156; 3 microM and 1 microM respectively) induced significant relaxation (39.0+/-8.7, 30.4+/-6.0 and 36.3+/-2.8 respectively). IBMX, dipyridamole and T0156 produced similar relaxation on 5-HT-induced contraction. After forskolin, the addition of IBMX or rolipram increased the effect of the adenylate cyclase stimulator and almost completely relaxed the human umbilical artery contracted by histamine (92.5+/-4.9 and 90.9+/-4.7 respectively), suggesting a main role of PDE4. The data obtained with 5-HT contracted arteries confirmed this, because only rolipram and IBMX significantly increased the forskolin vasodilator effect. The administration of dipyridamole and T0156 after sodium nitroprusside (SNP) induced a significant increase of the SNP relaxant effect on histamine-contracted arteries, but PDE1 and PDE3 inhibition did not increase the effect of the guanylate cyclase stimulator. Similar effects were obtained in 5-HT contracted arteries, the SNP induced relaxation was increased by the PDE5 inhibition, but not by PDE1 or PDE3 inhibition. In summary, our results demonstrate that: 1) the increase of cAMP and/or cGMP levels induces relaxation of the human umbilical vascular smooth muscle; 2) four families of PDE are expressed in this smooth muscle: PDE1, PDE3, PDE4 and PDE5; 3) between these families, PDE4 and PDE5 are the key enzymes involved in the regulation of the relaxation associated to cAMP and cGMP, respectively.

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“…However, obtaining data on the trans-stimulated status in critical in such case as levels of analogs may change under different conditions [21,25,26]. Data are expressed as means ± SD (n = 6); influx in lmol/L of cells/h; * ANOVA P \ 0.05 Previous studies have evaluated the L-arginine/nitric oxide pathway [22,23,25,26,32], and an L-arginine paradox has been often referred [33,34] to-exogenous L-arginine causing NO-mediated biological effects, despite nitric oxide synthases theoretical saturation with substrate [33]. Yet y?L L-arginine activity up-regulation [29] could explain such paradox.…”

Section: Discussionmentioning

confidence: 99%

Erythrocytes l-Arginine y+ Transporter Inhibition by N-Ethylmaleimide in Ice-bath

Costa

Almeida

Conceição

et al. 2010

Cell Biochem Biophys

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Erythrocytes L: -arginine uptake is conveyed by y+ and y+L membrane transport systems. Pre-incubation with N-ethylmaleimide for 10 min at 37°C inhibits the y+ system. The aim of this study was to determine the ideal pre-incubation temperature in evaluating y+ and y+L systems. Cells were pre-incubated with or without N-ethylmaleimide for 10 min at 4°C and 37°C. L: -Arginine uptake was quantified by radioisotope and standard erythrocytes membrane flux methodology. Results demonstrate that erythrocytes L: -arginine content is depleted by pre-incubation at 37°C for 10 min, thus changing the V (max) measurement. The inhibitory effect of N-ethylmaleimide pre-incubation was temperature independent and already complete after 1 min of incubation. No significant difference in kinetic parameters was detected between cells pre-incubated at 37°C or 4°C, under zero-trans conditions. In conclusion, we suggest that measurement of erythrocytes L: -arginine uptake by y+ and y+L systems could be carried out without N-ethylmaleimide pre-incubation at 37°C.

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Maternal medicine: Increased serum phosphodiesterase activity in women with pre‐eclampsia

Cited by 18 publications

References 12 publications

Effects of Sildenafil in Nω-Nitro-l-Arginine Methyl Ester-Induced Intrauterine Growth Restriction in a Rat Model

Effects of Sildenafil in Nω-Nitro-l-Arginine Methyl Ester-Induced Intrauterine Growth Restriction in a Rat Model

PDE4 and PDE5 regulate cyclic nucleotides relaxing effects in human umbilical arteries

Erythrocytes l-Arginine y+ Transporter Inhibition by N-Ethylmaleimide in Ice-bath

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