Role of cGMP and cAMP in the hemodynamic response to intrathecal sildenafil administration

Detalhes bibliográficos
Autor(a) principal: Bombarda, Gabriela
Data de Publicação: 2011
Outros Autores: Sabino, João Paulo J., Silva, Carlos Alberto A. da, Fazan Jr., Rubens, Salgado, Maria Cristina O., Salgado, Helio C.
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.
id USP-19_ba09dc46a2d35cb80f795f4837cb078d
oai_identifier_str oai:revistas.usp.br:article/19267
network_acronym_str USP-19
network_name_str Clinics
repository_id_str
spelling 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