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Nebivolol Dilates Human Penile Arteries and Reverses Erectile Dysfunction in Diabetic Rats through Enhancement of Nitric Oxide Signaling
Traditional beta-blockers have sometimes been associated with erectile dysfunction (ED). Nebivolol is a cardioselective β1-adrenoceptor antagonist that promotes vasodilation through a nitric oxide (NO)-dependent mechanism. We evaluated the effects of nebivolol on the NO/cyclic guanosine monophosphat...
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Published in: | Journal of sexual medicine 2010-08, Vol.7 (8), p.2681-2697 |
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creator | Angulo, Javier Wright, Harold M. Cuevas, Pedro González-Corrochano, Rocío Fernández, Argentina Cuevas, Begoña La Fuente, José M. Gupta, Sandeep Sáenz de Tejada, Iñigo |
description | Traditional beta-blockers have sometimes been associated with erectile dysfunction (ED). Nebivolol is a cardioselective β1-adrenoceptor antagonist that promotes vasodilation through a nitric oxide (NO)-dependent mechanism.
We evaluated the effects of nebivolol on the NO/cyclic guanosine monophosphate (cGMP) signaling pathway, on erectile function and dysfunction, and in human penile vascular tissues.
Erectile response to cavernosal nerve electrical stimulation in control and diabetes-induced ED rats were evaluated, along with serum nitrite/nitrate (NOx) concentration and plasma/tissue cGMP levels. Endothelium-dependent and sildenafil-induced relaxation of isolated human corpus cavernosum (HCC) and human penile resistance arteries (HPRA) were also determined.
The effects of nebivolol on erectile function and dysfunction and on NO/cGMP-mediated responses.
Treatment with nebivolol significantly potentiated erectile response in control rats, regardless of its effects on blood pressure. Nebivolol increased NOx and plasma cGMP by 3-fold and 2.75-fold, respectively, and significantly augmented the elevation of plasma cGMP produced by sildenafil. Nebivolol enhanced endothelium-dependent and sildenafil-induced relaxations of HCC tissue, and produced endothelium-dependent vasodilation of HPRA. Nebivolol, but not atenolol, significantly improved erectile response in diabetic rats (51.6%, 53.2%, and 87.1% of response at 3Hz in nondiabetic rats, for vehicle-treated, atenolol-treated, and nebivolol-treated diabetic rats, respectively); after sildenafil administration, ED was completely reversed in nebivolol-treated diabetic rats (69.6% and 112% for diabetic rats treated with sildenafil and nebivolol plus sildenafil, respectively). Accordingly, nebivolol restored systemic NOx levels and cGMP content in penile tissue from these animals.
Nebivolol in vivo activated the NO/cGMP pathway, enhanced erectile response and reversed ED in diabetic rats. Moreover, nebivolol in vitro potentiated NO/cGMP-mediated relaxation of human erectile tissues. These effects may account for the low incidence of ED in nebivolol-treated hypertensive patients. Nebivolol therefore may have utility in the treatment of ED, particularly ED associated with diabetes. Angulo J, Wright HM, Cuevas P, González-Corrochano R, Fernández A, Cuevas B, La Fuente JM, Gupta S, and de Tejada IS. Nebivolol dilates human penile arteries and reverses erectile dysfunction in diabetic rats through enhancement of nitric o |
doi_str_mv | 10.1111/j.1743-6109.2010.01710.x |
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We evaluated the effects of nebivolol on the NO/cyclic guanosine monophosphate (cGMP) signaling pathway, on erectile function and dysfunction, and in human penile vascular tissues.
Erectile response to cavernosal nerve electrical stimulation in control and diabetes-induced ED rats were evaluated, along with serum nitrite/nitrate (NOx) concentration and plasma/tissue cGMP levels. Endothelium-dependent and sildenafil-induced relaxation of isolated human corpus cavernosum (HCC) and human penile resistance arteries (HPRA) were also determined.
The effects of nebivolol on erectile function and dysfunction and on NO/cGMP-mediated responses.
Treatment with nebivolol significantly potentiated erectile response in control rats, regardless of its effects on blood pressure. Nebivolol increased NOx and plasma cGMP by 3-fold and 2.75-fold, respectively, and significantly augmented the elevation of plasma cGMP produced by sildenafil. Nebivolol enhanced endothelium-dependent and sildenafil-induced relaxations of HCC tissue, and produced endothelium-dependent vasodilation of HPRA. Nebivolol, but not atenolol, significantly improved erectile response in diabetic rats (51.6%, 53.2%, and 87.1% of response at 3Hz in nondiabetic rats, for vehicle-treated, atenolol-treated, and nebivolol-treated diabetic rats, respectively); after sildenafil administration, ED was completely reversed in nebivolol-treated diabetic rats (69.6% and 112% for diabetic rats treated with sildenafil and nebivolol plus sildenafil, respectively). Accordingly, nebivolol restored systemic NOx levels and cGMP content in penile tissue from these animals.
Nebivolol in vivo activated the NO/cGMP pathway, enhanced erectile response and reversed ED in diabetic rats. Moreover, nebivolol in vitro potentiated NO/cGMP-mediated relaxation of human erectile tissues. These effects may account for the low incidence of ED in nebivolol-treated hypertensive patients. Nebivolol therefore may have utility in the treatment of ED, particularly ED associated with diabetes. Angulo J, Wright HM, Cuevas P, González-Corrochano R, Fernández A, Cuevas B, La Fuente JM, Gupta S, and de Tejada IS. Nebivolol dilates human penile arteries and reverses erectile dysfunction in diabetic rats through enhancement of nitric oxide signaling.</description><identifier>ISSN: 1743-6095</identifier><identifier>EISSN: 1743-6109</identifier><identifier>DOI: 10.1111/j.1743-6109.2010.01710.x</identifier><identifier>PMID: 20214719</identifier><language>eng</language><publisher>Malden, USA: Elsevier Inc</publisher><subject>Animals ; Atenolol - pharmacology ; Benzopyrans - pharmacology ; Blood Glucose - metabolism ; Blood Pressure - drug effects ; Cyclic GMP - physiology ; Diabetes ; Diabetes Mellitus, Experimental - physiopathology ; Dose-Response Relationship, Drug ; Endothelium, Vascular - drug effects ; Erectile Dysfunction - physiopathology ; Erectile Dysfunction and Hypertensive Agents ; Ethanolamines - pharmacology ; Heart Rate - drug effects ; Humans ; In Vitro Techniques ; Injections, Intravenous ; Male ; Nebivolol ; Nitric Oxide ; Nitric Oxide - physiology ; Penis - blood supply ; Piperazines - pharmacology ; Purines - pharmacology ; Rats ; Rats, Sprague-Dawley ; Signal Transduction - drug effects ; Sildenafil Citrate ; Sulfones - pharmacology ; Sympatholytics - pharmacology ; Type 5 Phosphodiesterase Inhibitors ; Vascular Resistance - drug effects ; Vasodilator Agents - pharmacology ; β-Blockers</subject><ispartof>Journal of sexual medicine, 2010-08, Vol.7 (8), p.2681-2697</ispartof><rights>2010 International Society for Sexual Medicine</rights><rights>2010 International Society for Sexual Medicine.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4650-c050ccaac7a4e93a22346ca09f4f0c65175d7a0d26a8cbfc57075a06b98339673</citedby><cites>FETCH-LOGICAL-c4650-c050ccaac7a4e93a22346ca09f4f0c65175d7a0d26a8cbfc57075a06b98339673</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1743-6109.2010.01710.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1743-6109.2010.01710.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,786,790,1424,27957,27958,45609,45610</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20214719$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Angulo, Javier</creatorcontrib><creatorcontrib>Wright, Harold M.</creatorcontrib><creatorcontrib>Cuevas, Pedro</creatorcontrib><creatorcontrib>González-Corrochano, Rocío</creatorcontrib><creatorcontrib>Fernández, Argentina</creatorcontrib><creatorcontrib>Cuevas, Begoña</creatorcontrib><creatorcontrib>La Fuente, José M.</creatorcontrib><creatorcontrib>Gupta, Sandeep</creatorcontrib><creatorcontrib>Sáenz de Tejada, Iñigo</creatorcontrib><title>Nebivolol Dilates Human Penile Arteries and Reverses Erectile Dysfunction in Diabetic Rats through Enhancement of Nitric Oxide Signaling</title><title>Journal of sexual medicine</title><addtitle>J Sex Med</addtitle><description>Traditional beta-blockers have sometimes been associated with erectile dysfunction (ED). Nebivolol is a cardioselective β1-adrenoceptor antagonist that promotes vasodilation through a nitric oxide (NO)-dependent mechanism.
We evaluated the effects of nebivolol on the NO/cyclic guanosine monophosphate (cGMP) signaling pathway, on erectile function and dysfunction, and in human penile vascular tissues.
Erectile response to cavernosal nerve electrical stimulation in control and diabetes-induced ED rats were evaluated, along with serum nitrite/nitrate (NOx) concentration and plasma/tissue cGMP levels. Endothelium-dependent and sildenafil-induced relaxation of isolated human corpus cavernosum (HCC) and human penile resistance arteries (HPRA) were also determined.
The effects of nebivolol on erectile function and dysfunction and on NO/cGMP-mediated responses.
Treatment with nebivolol significantly potentiated erectile response in control rats, regardless of its effects on blood pressure. Nebivolol increased NOx and plasma cGMP by 3-fold and 2.75-fold, respectively, and significantly augmented the elevation of plasma cGMP produced by sildenafil. Nebivolol enhanced endothelium-dependent and sildenafil-induced relaxations of HCC tissue, and produced endothelium-dependent vasodilation of HPRA. Nebivolol, but not atenolol, significantly improved erectile response in diabetic rats (51.6%, 53.2%, and 87.1% of response at 3Hz in nondiabetic rats, for vehicle-treated, atenolol-treated, and nebivolol-treated diabetic rats, respectively); after sildenafil administration, ED was completely reversed in nebivolol-treated diabetic rats (69.6% and 112% for diabetic rats treated with sildenafil and nebivolol plus sildenafil, respectively). Accordingly, nebivolol restored systemic NOx levels and cGMP content in penile tissue from these animals.
Nebivolol in vivo activated the NO/cGMP pathway, enhanced erectile response and reversed ED in diabetic rats. Moreover, nebivolol in vitro potentiated NO/cGMP-mediated relaxation of human erectile tissues. These effects may account for the low incidence of ED in nebivolol-treated hypertensive patients. Nebivolol therefore may have utility in the treatment of ED, particularly ED associated with diabetes. Angulo J, Wright HM, Cuevas P, González-Corrochano R, Fernández A, Cuevas B, La Fuente JM, Gupta S, and de Tejada IS. Nebivolol dilates human penile arteries and reverses erectile dysfunction in diabetic rats through enhancement of nitric oxide signaling.</description><subject>Animals</subject><subject>Atenolol - pharmacology</subject><subject>Benzopyrans - pharmacology</subject><subject>Blood Glucose - metabolism</subject><subject>Blood Pressure - drug effects</subject><subject>Cyclic GMP - physiology</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Experimental - physiopathology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Erectile Dysfunction - physiopathology</subject><subject>Erectile Dysfunction and Hypertensive Agents</subject><subject>Ethanolamines - pharmacology</subject><subject>Heart Rate - drug effects</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Injections, Intravenous</subject><subject>Male</subject><subject>Nebivolol</subject><subject>Nitric Oxide</subject><subject>Nitric Oxide - physiology</subject><subject>Penis - blood supply</subject><subject>Piperazines - pharmacology</subject><subject>Purines - pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Signal Transduction - drug effects</subject><subject>Sildenafil Citrate</subject><subject>Sulfones - pharmacology</subject><subject>Sympatholytics - pharmacology</subject><subject>Type 5 Phosphodiesterase Inhibitors</subject><subject>Vascular Resistance - drug effects</subject><subject>Vasodilator Agents - pharmacology</subject><subject>β-Blockers</subject><issn>1743-6095</issn><issn>1743-6109</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><recordid>eNqNUU1z0zAQ1TAwtAT-AqMbJwf5U_GBQ2nTFAgp08Bw1KzldaJgS0WSQ_IP-NnIuM0V9iCtdt9bzb5HCI3ZNA7xdjeNeZZGRczKacJClcU8nIcn5PzUePqYszI_Iy-c2zGWhkiek7OEJXHG4_Kc_F5hpfamNS29Ui14dPSm70DTL6hVi_TCerQqVEHX9A73aF14zC1KP7Svjq7pdciNpkqHEVChV5LegXfUb63pN1s611vQEjvUnpqGrpS3AXJ7UDXStdpoaJXevCTPGmgdvnq4J-Tb9fzr5U20vF18uLxYRjIrchZJljMpASSHDMsUkiTNCgmsbLKGySKPeV5zYHVSwExWjcw54zmwoipnaVoWPJ2QN-Pce2t-9ui86JST2Lag0fROzHiWlGUa5k7IbERKa5yz2Ih7qzqwRxEzMdggdmJQWAxqi8EG8dcGcQjU1w-f9FWH9Yn4qHsAvBsBv4KKx_8eLD6uPw9Z4EcjXzmPhxMf7A8RduS5-L5aiGyRrPmnJRfXAf9-xGOQdq_QCicVBlNqNVgpaqP-vdUfuvi7og</recordid><startdate>201008</startdate><enddate>201008</enddate><creator>Angulo, Javier</creator><creator>Wright, Harold M.</creator><creator>Cuevas, Pedro</creator><creator>González-Corrochano, Rocío</creator><creator>Fernández, Argentina</creator><creator>Cuevas, Begoña</creator><creator>La Fuente, José M.</creator><creator>Gupta, Sandeep</creator><creator>Sáenz de Tejada, Iñigo</creator><general>Elsevier Inc</general><general>Blackwell Publishing Inc</general><scope>BSCLL</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>201008</creationdate><title>Nebivolol Dilates Human Penile Arteries and Reverses Erectile Dysfunction in Diabetic Rats through Enhancement of Nitric Oxide Signaling</title><author>Angulo, Javier ; Wright, Harold M. ; Cuevas, Pedro ; González-Corrochano, Rocío ; Fernández, Argentina ; Cuevas, Begoña ; La Fuente, José M. ; Gupta, Sandeep ; Sáenz de Tejada, Iñigo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4650-c050ccaac7a4e93a22346ca09f4f0c65175d7a0d26a8cbfc57075a06b98339673</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Atenolol - pharmacology</topic><topic>Benzopyrans - pharmacology</topic><topic>Blood Glucose - metabolism</topic><topic>Blood Pressure - drug effects</topic><topic>Cyclic GMP - physiology</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Experimental - physiopathology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Erectile Dysfunction - physiopathology</topic><topic>Erectile Dysfunction and Hypertensive Agents</topic><topic>Ethanolamines - pharmacology</topic><topic>Heart Rate - drug effects</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Injections, Intravenous</topic><topic>Male</topic><topic>Nebivolol</topic><topic>Nitric Oxide</topic><topic>Nitric Oxide - physiology</topic><topic>Penis - blood supply</topic><topic>Piperazines - pharmacology</topic><topic>Purines - pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Signal Transduction - drug effects</topic><topic>Sildenafil Citrate</topic><topic>Sulfones - pharmacology</topic><topic>Sympatholytics - pharmacology</topic><topic>Type 5 Phosphodiesterase Inhibitors</topic><topic>Vascular Resistance - drug effects</topic><topic>Vasodilator Agents - pharmacology</topic><topic>β-Blockers</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Angulo, Javier</creatorcontrib><creatorcontrib>Wright, Harold M.</creatorcontrib><creatorcontrib>Cuevas, Pedro</creatorcontrib><creatorcontrib>González-Corrochano, Rocío</creatorcontrib><creatorcontrib>Fernández, Argentina</creatorcontrib><creatorcontrib>Cuevas, Begoña</creatorcontrib><creatorcontrib>La Fuente, José M.</creatorcontrib><creatorcontrib>Gupta, Sandeep</creatorcontrib><creatorcontrib>Sáenz de Tejada, Iñigo</creatorcontrib><collection>Istex</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>Journal of sexual medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Angulo, Javier</au><au>Wright, Harold M.</au><au>Cuevas, Pedro</au><au>González-Corrochano, Rocío</au><au>Fernández, Argentina</au><au>Cuevas, Begoña</au><au>La Fuente, José M.</au><au>Gupta, Sandeep</au><au>Sáenz de Tejada, Iñigo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nebivolol Dilates Human Penile Arteries and Reverses Erectile Dysfunction in Diabetic Rats through Enhancement of Nitric Oxide Signaling</atitle><jtitle>Journal of sexual medicine</jtitle><addtitle>J Sex Med</addtitle><date>2010-08</date><risdate>2010</risdate><volume>7</volume><issue>8</issue><spage>2681</spage><epage>2697</epage><pages>2681-2697</pages><issn>1743-6095</issn><eissn>1743-6109</eissn><notes>ArticleID:JSM1710</notes><notes>ark:/67375/WNG-4G2S7KL7-F</notes><notes>istex:A134D8766DA05D7C327A658832C589693D280671</notes><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Traditional beta-blockers have sometimes been associated with erectile dysfunction (ED). Nebivolol is a cardioselective β1-adrenoceptor antagonist that promotes vasodilation through a nitric oxide (NO)-dependent mechanism.
We evaluated the effects of nebivolol on the NO/cyclic guanosine monophosphate (cGMP) signaling pathway, on erectile function and dysfunction, and in human penile vascular tissues.
Erectile response to cavernosal nerve electrical stimulation in control and diabetes-induced ED rats were evaluated, along with serum nitrite/nitrate (NOx) concentration and plasma/tissue cGMP levels. Endothelium-dependent and sildenafil-induced relaxation of isolated human corpus cavernosum (HCC) and human penile resistance arteries (HPRA) were also determined.
The effects of nebivolol on erectile function and dysfunction and on NO/cGMP-mediated responses.
Treatment with nebivolol significantly potentiated erectile response in control rats, regardless of its effects on blood pressure. Nebivolol increased NOx and plasma cGMP by 3-fold and 2.75-fold, respectively, and significantly augmented the elevation of plasma cGMP produced by sildenafil. Nebivolol enhanced endothelium-dependent and sildenafil-induced relaxations of HCC tissue, and produced endothelium-dependent vasodilation of HPRA. Nebivolol, but not atenolol, significantly improved erectile response in diabetic rats (51.6%, 53.2%, and 87.1% of response at 3Hz in nondiabetic rats, for vehicle-treated, atenolol-treated, and nebivolol-treated diabetic rats, respectively); after sildenafil administration, ED was completely reversed in nebivolol-treated diabetic rats (69.6% and 112% for diabetic rats treated with sildenafil and nebivolol plus sildenafil, respectively). Accordingly, nebivolol restored systemic NOx levels and cGMP content in penile tissue from these animals.
Nebivolol in vivo activated the NO/cGMP pathway, enhanced erectile response and reversed ED in diabetic rats. Moreover, nebivolol in vitro potentiated NO/cGMP-mediated relaxation of human erectile tissues. These effects may account for the low incidence of ED in nebivolol-treated hypertensive patients. Nebivolol therefore may have utility in the treatment of ED, particularly ED associated with diabetes. Angulo J, Wright HM, Cuevas P, González-Corrochano R, Fernández A, Cuevas B, La Fuente JM, Gupta S, and de Tejada IS. Nebivolol dilates human penile arteries and reverses erectile dysfunction in diabetic rats through enhancement of nitric oxide signaling.</abstract><cop>Malden, USA</cop><pub>Elsevier Inc</pub><pmid>20214719</pmid><doi>10.1111/j.1743-6109.2010.01710.x</doi><tpages>17</tpages></addata></record> |
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subjects | Animals Atenolol - pharmacology Benzopyrans - pharmacology Blood Glucose - metabolism Blood Pressure - drug effects Cyclic GMP - physiology Diabetes Diabetes Mellitus, Experimental - physiopathology Dose-Response Relationship, Drug Endothelium, Vascular - drug effects Erectile Dysfunction - physiopathology Erectile Dysfunction and Hypertensive Agents Ethanolamines - pharmacology Heart Rate - drug effects Humans In Vitro Techniques Injections, Intravenous Male Nebivolol Nitric Oxide Nitric Oxide - physiology Penis - blood supply Piperazines - pharmacology Purines - pharmacology Rats Rats, Sprague-Dawley Signal Transduction - drug effects Sildenafil Citrate Sulfones - pharmacology Sympatholytics - pharmacology Type 5 Phosphodiesterase Inhibitors Vascular Resistance - drug effects Vasodilator Agents - pharmacology β-Blockers |
title | Nebivolol Dilates Human Penile Arteries and Reverses Erectile Dysfunction in Diabetic Rats through Enhancement of Nitric Oxide Signaling |
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