The Mechanism of Action of Phosphodiesterase Type 5 Inhibitors in the Treatment of Lower Urinary Tract Symptoms Related to Benign Prostatic Hyperplasia
Identifieur interne : 000430 ( France/Analysis ); précédent : 000429; suivant : 000431The Mechanism of Action of Phosphodiesterase Type 5 Inhibitors in the Treatment of Lower Urinary Tract Symptoms Related to Benign Prostatic Hyperplasia
Auteurs : François Giuliano [France] ; Stefan Ückert [Allemagne] ; Mario Maggi [Italie] ; Lori Birder [États-Unis] ; Jay Kissel [États-Unis] ; Lars Viktrup [États-Unis]Source :
- European urology [ 0302-2838 ] ; 2013.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
Context: Clinical trials of phosphodiesterase type 5 inhibitors (PDE5-Is) have consistently demonstrated a significant reduction in lower urinary tract symptoms (LUTS) and small urinary flow rate changes in men with benign prostatic hyperplasia (BPH). Objective: This review presents the proposed mechanisms of action of PDE5-Is in the treatment of BPH-LUTS focusing on the localization of PDE5 isoenzymes in the pelvic structures; smooth muscle relaxation in the bladder, prostate, and supporting vasculature; increased blood perfusion of the bladder and prostate; and modulation of sensory impulses from these organs. Evidence acquisition: Literature describing in vitro, preclinical, or clinical studies of pathologic processes contributing to LUTS or effects of PDE5 inhibition on the lower urinary tract (LUT) was selected for review. Evidence synthesis: We objectively assessed and summarized the published data focusing on articles published within the past 10 yr. Articles before the time cut-off were included if historically relevant. Conclusions: The PDE5 isoenzymes are highly expressed in the LUT including the bladder, prostate, and their supporting vasculature. In vitro assays have demonstrated PDE5-Is by regulating cyclic guanosine monophosphate (cGMP) degradation and enhancing the nitric oxide/cGMP signaling pathway to relax human smooth muscle strips from the prostate, bladder, and LUT arteries. In animals characterized by ischemia/ hypoxia of the genitourinary tract, treatment with PDE5-Is increases bladder and prostate tissue oxygenation. PDE5-Is have been shown to reduce nonvoiding contractions and bladder afferent nerve firing in decerebrate spinal cord-injured rats, and to reduce mechanosensitive afferent activities of both Aδ- and C-fibers in an irritated or overextended bladder model.
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">The Mechanism of Action of Phosphodiesterase Type 5 Inhibitors in the Treatment of Lower Urinary Tract Symptoms Related to Benign Prostatic Hyperplasia</title><author><name sortKey="Giuliano, Francois" sort="Giuliano, Francois" uniqKey="Giuliano F" first="François" last="Giuliano">François Giuliano</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Neuro-Uro-Andrology Department of Physical Medicine and Rehabilitation, Raymond Poincaré Academic Hospital, Garches, Versailles Saint Quentin en Yvelines University</s1><s2>Garches</s2><s3>FRA</s3><sZ>1 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>Garches</wicri:noRegion><wicri:noRegion>Versailles Saint Quentin en Yvelines University</wicri:noRegion><wicri:noRegion>Garches</wicri:noRegion></affiliation></author><author><name sortKey="Uckert, Stefan" sort="Uckert, Stefan" uniqKey="Uckert S" first="Stefan" last="Ückert">Stefan Ückert</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Hannover Medical School, Division of Surgery, Department of Urology & Urological Oncology</s1><s2>Hannover</s2><s3>DEU</s3><sZ>2 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="2">Basse-Saxe</region><settlement type="city">Hanovre</settlement></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Institute for Biochemical Research and Analysis, Urological Research Unit</s1><s2>Barsinghausen</s2><s3>DEU</s3><sZ>2 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Barsinghausen</wicri:noRegion><wicri:noRegion>Urological Research Unit</wicri:noRegion><wicri:noRegion>Barsinghausen</wicri:noRegion></affiliation></author><author><name sortKey="Maggi, Mario" sort="Maggi, Mario" uniqKey="Maggi M" first="Mario" last="Maggi">Mario Maggi</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Sexual Medicine and Andrology Unit, Department of Clinical 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aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>Garches</wicri:noRegion><wicri:noRegion>Versailles Saint Quentin en Yvelines University</wicri:noRegion><wicri:noRegion>Garches</wicri:noRegion></affiliation></author><author><name sortKey="Uckert, Stefan" sort="Uckert, Stefan" uniqKey="Uckert S" first="Stefan" last="Ückert">Stefan Ückert</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Hannover Medical School, Division of Surgery, Department of Urology & Urological Oncology</s1><s2>Hannover</s2><s3>DEU</s3><sZ>2 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="2">Basse-Saxe</region><settlement type="city">Hanovre</settlement></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Institute for Biochemical Research and Analysis, Urological Research Unit</s1><s2>Barsinghausen</s2><s3>DEU</s3><sZ>2 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Barsinghausen</wicri:noRegion><wicri:noRegion>Urological Research Unit</wicri:noRegion><wicri:noRegion>Barsinghausen</wicri:noRegion></affiliation></author><author><name sortKey="Maggi, Mario" sort="Maggi, Mario" uniqKey="Maggi M" first="Mario" last="Maggi">Mario Maggi</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Sexual Medicine and Andrology Unit, Department of Clinical Physiopathology, University of Florence</s1><s2>Florence</s2><s3>ITA</s3><sZ>3 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Florence</wicri:noRegion></affiliation></author><author><name sortKey="Birder, Lori" sort="Birder, Lori" uniqKey="Birder L" first="Lori" last="Birder">Lori Birder</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Medicine and Pharmacology, University of Pittsburgh School of Medicine</s1><s2>Pittsburgh, PA</s2><s3>USA</s3><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Pittsburgh, PA</wicri:noRegion></affiliation></author><author><name sortKey="Kissel, Jay" sort="Kissel, Jay" uniqKey="Kissel J" first="Jay" last="Kissel">Jay Kissel</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Lilly Research Laboratories, Eli Lilly and Company</s1><s2>Indianapolis, IN</s2><s3>USA</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Indianapolis, IN</wicri:noRegion></affiliation></author><author><name sortKey="Viktrup, Lars" sort="Viktrup, Lars" uniqKey="Viktrup L" first="Lars" last="Viktrup">Lars Viktrup</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Lilly Research Laboratories, Eli Lilly and Company</s1><s2>Indianapolis, IN</s2><s3>USA</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Indianapolis, IN</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">European urology</title><title level="j" type="abbreviated">Eur. urol.</title><idno type="ISSN">0302-2838</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">European urology</title><title level="j" type="abbreviated">Eur. urol.</title><idno type="ISSN">0302-2838</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>3′,5′-Cyclic-nucleotide phosphodiesterase</term><term>Benign prostatic hyperplasia</term><term>Inhibitor</term><term>Lower urinary tract symptoms</term><term>Mechanism of action</term><term>Nephrology</term><term>Treatment</term><term>Urology</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Troubles urinaires du bas appareil</term><term>Mécanisme action</term><term>3′,5′-Cyclic-nucleotide phosphodiesterase</term><term>Adénome de la prostate</term><term>Inhibiteur</term><term>Traitement</term><term>Néphrologie</term><term>Urologie</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Context: Clinical trials of phosphodiesterase type 5 inhibitors (PDE5-Is) have consistently demonstrated a significant reduction in lower urinary tract symptoms (LUTS) and small urinary flow rate changes in men with benign prostatic hyperplasia (BPH). Objective: This review presents the proposed mechanisms of action of PDE5-Is in the treatment of BPH-LUTS focusing on the localization of PDE5 isoenzymes in the pelvic structures; smooth muscle relaxation in the bladder, prostate, and supporting vasculature; increased blood perfusion of the bladder and prostate; and modulation of sensory impulses from these organs. Evidence acquisition: Literature describing in vitro, preclinical, or clinical studies of pathologic processes contributing to LUTS or effects of PDE5 inhibition on the lower urinary tract (LUT) was selected for review. Evidence synthesis: We objectively assessed and summarized the published data focusing on articles published within the past 10 yr. Articles before the time cut-off were included if historically relevant. Conclusions: The PDE5 isoenzymes are highly expressed in the LUT including the bladder, prostate, and their supporting vasculature. In vitro assays have demonstrated PDE5-Is by regulating cyclic guanosine monophosphate (cGMP) degradation and enhancing the nitric oxide/cGMP signaling pathway to relax human smooth muscle strips from the prostate, bladder, and LUT arteries. In animals characterized by ischemia/ hypoxia of the genitourinary tract, treatment with PDE5-Is increases bladder and prostate tissue oxygenation. PDE5-Is have been shown to reduce nonvoiding contractions and bladder afferent nerve firing in decerebrate spinal cord-injured rats, and to reduce mechanosensitive afferent activities of both Aδ- and C-fibers in an irritated or overextended bladder model.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>France</li><li>Italie</li><li>États-Unis</li></country><region><li>Basse-Saxe</li></region><settlement><li>Hanovre</li></settlement></list><tree><country name="France"><noRegion><name sortKey="Giuliano, Francois" sort="Giuliano, Francois" uniqKey="Giuliano F" first="François" last="Giuliano">François Giuliano</name></noRegion></country><country name="Allemagne"><region name="Basse-Saxe"><name sortKey="Uckert, Stefan" sort="Uckert, Stefan" uniqKey="Uckert S" first="Stefan" last="Ückert">Stefan Ückert</name></region><name sortKey="Uckert, Stefan" sort="Uckert, Stefan" uniqKey="Uckert S" first="Stefan" last="Ückert">Stefan Ückert</name></country><country name="Italie"><noRegion><name sortKey="Maggi, Mario" sort="Maggi, Mario" uniqKey="Maggi M" first="Mario" last="Maggi">Mario Maggi</name></noRegion></country><country name="États-Unis"><noRegion><name sortKey="Birder, Lori" sort="Birder, Lori" uniqKey="Birder L" first="Lori" last="Birder">Lori Birder</name></noRegion><name sortKey="Kissel, Jay" sort="Kissel, Jay" uniqKey="Kissel J" first="Jay" last="Kissel">Jay Kissel</name><name sortKey="Viktrup, Lars" sort="Viktrup, Lars" uniqKey="Viktrup L" first="Lars" last="Viktrup">Lars Viktrup</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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