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Does sildenafil citrate affect myometrial contractile response to nifedipine in vitro?

Objective We sought to test the hypothesis that sildenafil citrate (SC) at low concentrations potentiates the tocolytic effects of nifedipine in vitro. Study Design Myometrial biopsies were obtained from 22 term nonlaboring women undergoing scheduled cesarean delivery. Tissue strips were suspended i...

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Published in:American journal of obstetrics and gynecology 2010-09, Vol.203 (3), p.252.e1-252.e5
Main Authors: Chiossi, Giuseppe, MD, Costantine, Maged M., MD, Betancourt, Ancizar, MS, Hankins, Gary D.V., MD, Longo, Monica, MD, PhD, Saade, George R., MD, Bytautiene, Egle, MD, PhD
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container_title American journal of obstetrics and gynecology
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creator Chiossi, Giuseppe, MD
Costantine, Maged M., MD
Betancourt, Ancizar, MS
Hankins, Gary D.V., MD
Longo, Monica, MD, PhD
Saade, George R., MD
Bytautiene, Egle, MD, PhD
description Objective We sought to test the hypothesis that sildenafil citrate (SC) at low concentrations potentiates the tocolytic effects of nifedipine in vitro. Study Design Myometrial biopsies were obtained from 22 term nonlaboring women undergoing scheduled cesarean delivery. Tissue strips were suspended in organ chambers for isometric tension recording, and incubated for 30 minutes with either SC at 231 ng/mL or solvent. The effects of cumulative doses (10–10 to 10–5 mol/L) of nifedipine on spontaneous and oxytocin-induced uterine contractility were then determined. Areas under the contraction curve were compared using 1-way analysis of variance with Tukey post hoc test (significance: P < .05). Results Nifedipine significantly inhibited spontaneous and oxytocin-induced myometrial contractility. Preincubation with SC increased response to nifedipine and significantly potentiated its inhibitory effect at 10–8 mol/L, without affecting oxytocin-induced contractile response. Conclusion At concentrations within a therapeutic window, SC increases myometrial sensitivity to nifedipine.
doi_str_mv 10.1016/j.ajog.2010.05.007
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Study Design Myometrial biopsies were obtained from 22 term nonlaboring women undergoing scheduled cesarean delivery. Tissue strips were suspended in organ chambers for isometric tension recording, and incubated for 30 minutes with either SC at 231 ng/mL or solvent. The effects of cumulative doses (10–10 to 10–5 mol/L) of nifedipine on spontaneous and oxytocin-induced uterine contractility were then determined. Areas under the contraction curve were compared using 1-way analysis of variance with Tukey post hoc test (significance: P &lt; .05). Results Nifedipine significantly inhibited spontaneous and oxytocin-induced myometrial contractility. Preincubation with SC increased response to nifedipine and significantly potentiated its inhibitory effect at 10–8 mol/L, without affecting oxytocin-induced contractile response. Conclusion At concentrations within a therapeutic window, SC increases myometrial sensitivity to nifedipine.</description><identifier>ISSN: 0002-9378</identifier><identifier>EISSN: 1097-6868</identifier><identifier>DOI: 10.1016/j.ajog.2010.05.007</identifier><identifier>PMID: 20541728</identifier><identifier>CODEN: AJOGAH</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adult ; Antiarythmic agents ; Biological and medical sciences ; Biopsy ; Calcium Channel Blockers - pharmacology ; Cardiovascular system ; Female ; Gynecology. Andrology. Obstetrics ; Humans ; In Vitro Techniques ; Medical sciences ; Myometrium - drug effects ; Myometrium - pathology ; nifedipine ; Nifedipine - pharmacology ; Obstetrics and Gynecology ; organ chamber ; Oxytocics - pharmacology ; oxytocin ; Oxytocin - pharmacology ; Pharmacology. 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Study Design Myometrial biopsies were obtained from 22 term nonlaboring women undergoing scheduled cesarean delivery. Tissue strips were suspended in organ chambers for isometric tension recording, and incubated for 30 minutes with either SC at 231 ng/mL or solvent. The effects of cumulative doses (10–10 to 10–5 mol/L) of nifedipine on spontaneous and oxytocin-induced uterine contractility were then determined. Areas under the contraction curve were compared using 1-way analysis of variance with Tukey post hoc test (significance: P &lt; .05). Results Nifedipine significantly inhibited spontaneous and oxytocin-induced myometrial contractility. Preincubation with SC increased response to nifedipine and significantly potentiated its inhibitory effect at 10–8 mol/L, without affecting oxytocin-induced contractile response. Conclusion At concentrations within a therapeutic window, SC increases myometrial sensitivity to nifedipine.</description><subject>Adult</subject><subject>Antiarythmic agents</subject><subject>Biological and medical sciences</subject><subject>Biopsy</subject><subject>Calcium Channel Blockers - pharmacology</subject><subject>Cardiovascular system</subject><subject>Female</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Medical sciences</subject><subject>Myometrium - drug effects</subject><subject>Myometrium - pathology</subject><subject>nifedipine</subject><subject>Nifedipine - pharmacology</subject><subject>Obstetrics and Gynecology</subject><subject>organ chamber</subject><subject>Oxytocics - pharmacology</subject><subject>oxytocin</subject><subject>Oxytocin - pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Piperazines - pharmacology</subject><subject>Pregnancy</subject><subject>Purines - pharmacology</subject><subject>Sildenafil Citrate</subject><subject>Sulfones - pharmacology</subject><subject>uterine contractility</subject><subject>Uterine Contraction - drug effects</subject><subject>Vasodilator Agents - pharmacology</subject><issn>0002-9378</issn><issn>1097-6868</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><recordid>eNp9kUuLFDEURoMoTjv6B1xINuKq2pukUkmBKDKODxhw4WMb0qkbSVmVtEn1QP97U3SPggtXedzz3YRzCXnKYMuAdS_HrR3Tjy2HegFyC6DukQ2DXjWd7vR9sgEA3vRC6QvyqJRxPfKePyQXHGTLFNcb8v1dwkJLmAaM1oeJurBkuyC13qNb6HxMMy452FpJsZbcEiakGcs-xYJ0STQGj0PYh4g0RHpb8-nNY_LA26ngk_N6Sb69v_569bG5-fzh09Xbm8a1LSyNAM39YBUfwA8992ilsINXVmpQHQO9czvkzFvLdStcN-yYkByF0x4k515ckhenvvucfh2wLGYOxeE02YjpUIySou9l27JK8hPpciolozf7HGabj4aBWXWa0aw6zarTgDRVZw09O7c_7GYc_kTu_FXg-RmwxdnJZxtdKH85wbnSoqvcqxOHVcZtwGyKCxhdFZerZjOk8P9_vP4n7qYQQ33xJx6xjOmQY9VsmCncgPmyTnqdO6sbqbpW_AaO7akD</recordid><startdate>20100901</startdate><enddate>20100901</enddate><creator>Chiossi, Giuseppe, MD</creator><creator>Costantine, Maged M., MD</creator><creator>Betancourt, Ancizar, MS</creator><creator>Hankins, Gary D.V., MD</creator><creator>Longo, Monica, MD, PhD</creator><creator>Saade, George R., MD</creator><creator>Bytautiene, Egle, MD, PhD</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20100901</creationdate><title>Does sildenafil citrate affect myometrial contractile response to nifedipine in vitro?</title><author>Chiossi, Giuseppe, MD ; Costantine, Maged M., MD ; Betancourt, Ancizar, MS ; Hankins, Gary D.V., MD ; Longo, Monica, MD, PhD ; Saade, George R., MD ; Bytautiene, Egle, MD, PhD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c440t-3082fda72d0fd92fea53adf7a58076108bcbe21faa2843c6db1352e3c8f0522f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adult</topic><topic>Antiarythmic agents</topic><topic>Biological and medical sciences</topic><topic>Biopsy</topic><topic>Calcium Channel Blockers - pharmacology</topic><topic>Cardiovascular system</topic><topic>Female</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Medical sciences</topic><topic>Myometrium - drug effects</topic><topic>Myometrium - pathology</topic><topic>nifedipine</topic><topic>Nifedipine - pharmacology</topic><topic>Obstetrics and Gynecology</topic><topic>organ chamber</topic><topic>Oxytocics - pharmacology</topic><topic>oxytocin</topic><topic>Oxytocin - pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Piperazines - pharmacology</topic><topic>Pregnancy</topic><topic>Purines - pharmacology</topic><topic>Sildenafil Citrate</topic><topic>Sulfones - pharmacology</topic><topic>uterine contractility</topic><topic>Uterine Contraction - drug effects</topic><topic>Vasodilator Agents - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chiossi, Giuseppe, MD</creatorcontrib><creatorcontrib>Costantine, Maged M., MD</creatorcontrib><creatorcontrib>Betancourt, Ancizar, MS</creatorcontrib><creatorcontrib>Hankins, Gary D.V., MD</creatorcontrib><creatorcontrib>Longo, Monica, MD, PhD</creatorcontrib><creatorcontrib>Saade, George R., MD</creatorcontrib><creatorcontrib>Bytautiene, Egle, MD, PhD</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of obstetrics and gynecology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chiossi, Giuseppe, MD</au><au>Costantine, Maged M., MD</au><au>Betancourt, Ancizar, MS</au><au>Hankins, Gary D.V., MD</au><au>Longo, Monica, MD, PhD</au><au>Saade, George R., MD</au><au>Bytautiene, Egle, MD, PhD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Does sildenafil citrate affect myometrial contractile response to nifedipine in vitro?</atitle><jtitle>American journal of obstetrics and gynecology</jtitle><addtitle>Am J Obstet Gynecol</addtitle><date>2010-09-01</date><risdate>2010</risdate><volume>203</volume><issue>3</issue><spage>252.e1</spage><epage>252.e5</epage><pages>252.e1-252.e5</pages><issn>0002-9378</issn><eissn>1097-6868</eissn><coden>AJOGAH</coden><abstract>Objective We sought to test the hypothesis that sildenafil citrate (SC) at low concentrations potentiates the tocolytic effects of nifedipine in vitro. Study Design Myometrial biopsies were obtained from 22 term nonlaboring women undergoing scheduled cesarean delivery. Tissue strips were suspended in organ chambers for isometric tension recording, and incubated for 30 minutes with either SC at 231 ng/mL or solvent. The effects of cumulative doses (10–10 to 10–5 mol/L) of nifedipine on spontaneous and oxytocin-induced uterine contractility were then determined. Areas under the contraction curve were compared using 1-way analysis of variance with Tukey post hoc test (significance: P &lt; .05). Results Nifedipine significantly inhibited spontaneous and oxytocin-induced myometrial contractility. Preincubation with SC increased response to nifedipine and significantly potentiated its inhibitory effect at 10–8 mol/L, without affecting oxytocin-induced contractile response. Conclusion At concentrations within a therapeutic window, SC increases myometrial sensitivity to nifedipine.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>20541728</pmid><doi>10.1016/j.ajog.2010.05.007</doi><tpages>3</tpages></addata></record>
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subjects Adult
Antiarythmic agents
Biological and medical sciences
Biopsy
Calcium Channel Blockers - pharmacology
Cardiovascular system
Female
Gynecology. Andrology. Obstetrics
Humans
In Vitro Techniques
Medical sciences
Myometrium - drug effects
Myometrium - pathology
nifedipine
Nifedipine - pharmacology
Obstetrics and Gynecology
organ chamber
Oxytocics - pharmacology
oxytocin
Oxytocin - pharmacology
Pharmacology. Drug treatments
Piperazines - pharmacology
Pregnancy
Purines - pharmacology
Sildenafil Citrate
Sulfones - pharmacology
uterine contractility
Uterine Contraction - drug effects
Vasodilator Agents - pharmacology
title Does sildenafil citrate affect myometrial contractile response to nifedipine in vitro?
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