Role of cGMP and cAMP in the hemodynamic response to intrathecal sildenafil administration
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Clinics |
Texto Completo: | https://www.revistas.usp.br/clinics/article/view/19267 |
Resumo: | INTRODUCTION: Results from our laboratory have demonstrated that intracerebroventricular administration of sildenafil to conscious rats promoted a noticeable increase in both lumbar sympathetic activity and heart rate, with no change in the mean arterial pressure. The intracerebroventricular administration of sildenafil may have produced the hemodynamic effects by activating sympathetic preganglionic neurons in the supraspinal regions and spinal cord. It is well documented that sildenafil increases intracellular cGMP levels by inhibiting phosphodiesterase type 5 and increases cAMP levels by inhibiting other phosphodiesterases. OBJECTIVE: To examine and compare, in conscious rats, the hemodynamic response following the intrathecal administration of sildenafil, 8-bromo-cGMP (an analog of cGMP), forskolin (an activator of adenylate cyclase), or dibutyryl-cAMP (an analog of cAMP) in order to elucidate the possible role of the sympathetic preganglionic neurons in the observed hemodynamic response. RESULTS: The hemodynamic responses observed following intrathecal administration of the studied drugs demonstrated the following: 1) sildenafil increased the mean arterial pressure and heart rate in a dose-dependent manner, 2) increasing doses of 8-bromo-cGMP did not alter the mean arterial pressure and heart rate, 3) forskolin did not affect the mean arterial pressure but did increase the heart rate and 4) dibutyryl-cAMP increased the mean arterial pressure and heart rate, similar to the effect observed following the intrathecal injection of the highest dose of sildenafil. CONCLUSION: Overall, the findings of the current study suggest that the cardiovascular response following the intrathecal administration of sildenafil to conscious rats involves the inhibition of phosphodiesterases other than phosphodiesterase type 5 that increase the cAMP level and the activation of sympathetic preganglionic neurons. |
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Clinics |
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Role of cGMP and cAMP in the hemodynamic response to intrathecal sildenafil administration Sympathetic preganglionic neuronsLumbar sympathetic activityForskolinPhosphodiesterase 5Spinal cord INTRODUCTION: Results from our laboratory have demonstrated that intracerebroventricular administration of sildenafil to conscious rats promoted a noticeable increase in both lumbar sympathetic activity and heart rate, with no change in the mean arterial pressure. The intracerebroventricular administration of sildenafil may have produced the hemodynamic effects by activating sympathetic preganglionic neurons in the supraspinal regions and spinal cord. It is well documented that sildenafil increases intracellular cGMP levels by inhibiting phosphodiesterase type 5 and increases cAMP levels by inhibiting other phosphodiesterases. OBJECTIVE: To examine and compare, in conscious rats, the hemodynamic response following the intrathecal administration of sildenafil, 8-bromo-cGMP (an analog of cGMP), forskolin (an activator of adenylate cyclase), or dibutyryl-cAMP (an analog of cAMP) in order to elucidate the possible role of the sympathetic preganglionic neurons in the observed hemodynamic response. RESULTS: The hemodynamic responses observed following intrathecal administration of the studied drugs demonstrated the following: 1) sildenafil increased the mean arterial pressure and heart rate in a dose-dependent manner, 2) increasing doses of 8-bromo-cGMP did not alter the mean arterial pressure and heart rate, 3) forskolin did not affect the mean arterial pressure but did increase the heart rate and 4) dibutyryl-cAMP increased the mean arterial pressure and heart rate, similar to the effect observed following the intrathecal injection of the highest dose of sildenafil. CONCLUSION: Overall, the findings of the current study suggest that the cardiovascular response following the intrathecal administration of sildenafil to conscious rats involves the inhibition of phosphodiesterases other than phosphodiesterase type 5 that increase the cAMP level and the activation of sympathetic preganglionic neurons. Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo2011-01-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://www.revistas.usp.br/clinics/article/view/1926710.1590/S1807-59322011000800017Clinics; Vol. 66 No. 8 (2011); 1407-1412 Clinics; v. 66 n. 8 (2011); 1407-1412 Clinics; Vol. 66 Núm. 8 (2011); 1407-1412 1980-53221807-5932reponame:Clinicsinstname:Universidade de São Paulo (USP)instacron:USPenghttps://www.revistas.usp.br/clinics/article/view/19267/21330Bombarda, GabrielaSabino, João Paulo J.Silva, Carlos Alberto A. daFazan Jr., RubensSalgado, Maria Cristina O.Salgado, Helio C.info:eu-repo/semantics/openAccess2012-05-23T16:31:08Zoai:revistas.usp.br:article/19267Revistahttps://www.revistas.usp.br/clinicsPUBhttps://www.revistas.usp.br/clinics/oai||clinics@hc.fm.usp.br1980-53221807-5932opendoar:2012-05-23T16:31:08Clinics - Universidade de São Paulo (USP)false |
dc.title.none.fl_str_mv |
Role of cGMP and cAMP in the hemodynamic response to intrathecal sildenafil administration |
title |
Role of cGMP and cAMP in the hemodynamic response to intrathecal sildenafil administration |
spellingShingle |
Role of cGMP and cAMP in the hemodynamic response to intrathecal sildenafil administration Bombarda, Gabriela Sympathetic preganglionic neurons Lumbar sympathetic activity Forskolin Phosphodiesterase 5 Spinal cord |
title_short |
Role of cGMP and cAMP in the hemodynamic response to intrathecal sildenafil administration |
title_full |
Role of cGMP and cAMP in the hemodynamic response to intrathecal sildenafil administration |
title_fullStr |
Role of cGMP and cAMP in the hemodynamic response to intrathecal sildenafil administration |
title_full_unstemmed |
Role of cGMP and cAMP in the hemodynamic response to intrathecal sildenafil administration |
title_sort |
Role of cGMP and cAMP in the hemodynamic response to intrathecal sildenafil administration |
author |
Bombarda, Gabriela |
author_facet |
Bombarda, Gabriela Sabino, João Paulo J. Silva, Carlos Alberto A. da Fazan Jr., Rubens Salgado, Maria Cristina O. Salgado, Helio C. |
author_role |
author |
author2 |
Sabino, João Paulo J. Silva, Carlos Alberto A. da Fazan Jr., Rubens Salgado, Maria Cristina O. Salgado, Helio C. |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Bombarda, Gabriela Sabino, João Paulo J. Silva, Carlos Alberto A. da Fazan Jr., Rubens Salgado, Maria Cristina O. Salgado, Helio C. |
dc.subject.por.fl_str_mv |
Sympathetic preganglionic neurons Lumbar sympathetic activity Forskolin Phosphodiesterase 5 Spinal cord |
topic |
Sympathetic preganglionic neurons Lumbar sympathetic activity Forskolin Phosphodiesterase 5 Spinal cord |
description |
INTRODUCTION: Results from our laboratory have demonstrated that intracerebroventricular administration of sildenafil to conscious rats promoted a noticeable increase in both lumbar sympathetic activity and heart rate, with no change in the mean arterial pressure. The intracerebroventricular administration of sildenafil may have produced the hemodynamic effects by activating sympathetic preganglionic neurons in the supraspinal regions and spinal cord. It is well documented that sildenafil increases intracellular cGMP levels by inhibiting phosphodiesterase type 5 and increases cAMP levels by inhibiting other phosphodiesterases. OBJECTIVE: To examine and compare, in conscious rats, the hemodynamic response following the intrathecal administration of sildenafil, 8-bromo-cGMP (an analog of cGMP), forskolin (an activator of adenylate cyclase), or dibutyryl-cAMP (an analog of cAMP) in order to elucidate the possible role of the sympathetic preganglionic neurons in the observed hemodynamic response. RESULTS: The hemodynamic responses observed following intrathecal administration of the studied drugs demonstrated the following: 1) sildenafil increased the mean arterial pressure and heart rate in a dose-dependent manner, 2) increasing doses of 8-bromo-cGMP did not alter the mean arterial pressure and heart rate, 3) forskolin did not affect the mean arterial pressure but did increase the heart rate and 4) dibutyryl-cAMP increased the mean arterial pressure and heart rate, similar to the effect observed following the intrathecal injection of the highest dose of sildenafil. CONCLUSION: Overall, the findings of the current study suggest that the cardiovascular response following the intrathecal administration of sildenafil to conscious rats involves the inhibition of phosphodiesterases other than phosphodiesterase type 5 that increase the cAMP level and the activation of sympathetic preganglionic neurons. |
publishDate |
2011 |
dc.date.none.fl_str_mv |
2011-01-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://www.revistas.usp.br/clinics/article/view/19267 10.1590/S1807-59322011000800017 |
url |
https://www.revistas.usp.br/clinics/article/view/19267 |
identifier_str_mv |
10.1590/S1807-59322011000800017 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
https://www.revistas.usp.br/clinics/article/view/19267/21330 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo |
publisher.none.fl_str_mv |
Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo |
dc.source.none.fl_str_mv |
Clinics; Vol. 66 No. 8 (2011); 1407-1412 Clinics; v. 66 n. 8 (2011); 1407-1412 Clinics; Vol. 66 Núm. 8 (2011); 1407-1412 1980-5322 1807-5932 reponame:Clinics instname:Universidade de São Paulo (USP) instacron:USP |
instname_str |
Universidade de São Paulo (USP) |
instacron_str |
USP |
institution |
USP |
reponame_str |
Clinics |
collection |
Clinics |
repository.name.fl_str_mv |
Clinics - Universidade de São Paulo (USP) |
repository.mail.fl_str_mv |
||clinics@hc.fm.usp.br |
_version_ |
1800222756334206976 |