A novel experimental model of erectile dysfunction in rats with heart failure using volume overload.
Patients with heart failure (HF) display erectile dysfunction (ED). However, the pathophysiology of ED during HF remains poorly investigated.This study aimed to characterize the aortocaval fistula (ACF) rat model associated with HF as a novel experimental model of ED. We have undertaken molecular an...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5667775?pdf=render |
| _version_ | 1811216927599624192 |
|---|---|
| author | Fábio Henrique Silva Frederico José Reis Veiga Aline Gonçalves Mora Rodrigo Sader Heck Caroline Candida De Oliveira Alessandra Gambero Carla Fernanda Franco-Penteado Edson Antunes Jason D Gardner Fernanda Bruschi Marinho Priviero Mário Angelo Claudino |
| author_facet | Fábio Henrique Silva Frederico José Reis Veiga Aline Gonçalves Mora Rodrigo Sader Heck Caroline Candida De Oliveira Alessandra Gambero Carla Fernanda Franco-Penteado Edson Antunes Jason D Gardner Fernanda Bruschi Marinho Priviero Mário Angelo Claudino |
| author_sort | Fábio Henrique Silva |
| collection | DOAJ |
| description | Patients with heart failure (HF) display erectile dysfunction (ED). However, the pathophysiology of ED during HF remains poorly investigated.This study aimed to characterize the aortocaval fistula (ACF) rat model associated with HF as a novel experimental model of ED. We have undertaken molecular and functional studies to evaluate the alterations of the nitric oxide (NO) pathway, autonomic nervous system and oxidative stress in the penis.Male rats were submitted to ACF for HF induction. Intracavernosal pressure in anesthetized rats was evaluated. Concentration-response curves to contractile (phenylephrine) and relaxant agents (sodium nitroprusside; SNP), as well as to electrical field stimulation (EFS), were obtained in the cavernosal smooth muscle (CSM) strips from sham and HF rats. Protein expression of endothelial NO synthase (eNOS) and neuronal NO synthase (nNOS) and phosphodiestarese-5 in CSM were evaluated, as well as NOX2 (gp91phox) and superoxide dismutase (SOD) mRNA expression. SOD activity and thiobarbituric acid reactive substances (TBARs) were also performed in plasma.HF rats display erectile dysfunction represented by decreased ICP responses compared to sham rats. The neurogenic contractile responses elicited by EFS were greater in CSM from the HF group. Likewise, phenylephrine-induced contractions were greater in CSM from HF rats. Nitrergic response induced by EFS were decreased in the cavernosal tissue, along with lower eNOS, nNOS and phosphodiestarese-5 protein expressions. An increase of NOX2 and SOD mRNA expression in CSM and plasma TBARs of HF group were detected. Plasma SOD activity was decreased in HF rats.ED in HF rats is associated with decreased NO bioavailability in erectile tissue due to eNOS/nNOS dowregulation and NOX2 upregulation, as well as hypercontractility of the penis. This rat model of ACF could be a useful tool to evaluate the molecular alterations of ED associated with HF. |
| first_indexed | 2024-04-12T06:45:42Z |
| format | Article |
| id | doaj.art-2d1d0ac7840b48caa772682951f8dab2 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T06:45:42Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-2d1d0ac7840b48caa772682951f8dab22022-12-22T03:43:33ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-011211e018708310.1371/journal.pone.0187083A novel experimental model of erectile dysfunction in rats with heart failure using volume overload.Fábio Henrique SilvaFrederico José Reis VeigaAline Gonçalves MoraRodrigo Sader HeckCaroline Candida De OliveiraAlessandra GamberoCarla Fernanda Franco-PenteadoEdson AntunesJason D GardnerFernanda Bruschi Marinho PrivieroMário Angelo ClaudinoPatients with heart failure (HF) display erectile dysfunction (ED). However, the pathophysiology of ED during HF remains poorly investigated.This study aimed to characterize the aortocaval fistula (ACF) rat model associated with HF as a novel experimental model of ED. We have undertaken molecular and functional studies to evaluate the alterations of the nitric oxide (NO) pathway, autonomic nervous system and oxidative stress in the penis.Male rats were submitted to ACF for HF induction. Intracavernosal pressure in anesthetized rats was evaluated. Concentration-response curves to contractile (phenylephrine) and relaxant agents (sodium nitroprusside; SNP), as well as to electrical field stimulation (EFS), were obtained in the cavernosal smooth muscle (CSM) strips from sham and HF rats. Protein expression of endothelial NO synthase (eNOS) and neuronal NO synthase (nNOS) and phosphodiestarese-5 in CSM were evaluated, as well as NOX2 (gp91phox) and superoxide dismutase (SOD) mRNA expression. SOD activity and thiobarbituric acid reactive substances (TBARs) were also performed in plasma.HF rats display erectile dysfunction represented by decreased ICP responses compared to sham rats. The neurogenic contractile responses elicited by EFS were greater in CSM from the HF group. Likewise, phenylephrine-induced contractions were greater in CSM from HF rats. Nitrergic response induced by EFS were decreased in the cavernosal tissue, along with lower eNOS, nNOS and phosphodiestarese-5 protein expressions. An increase of NOX2 and SOD mRNA expression in CSM and plasma TBARs of HF group were detected. Plasma SOD activity was decreased in HF rats.ED in HF rats is associated with decreased NO bioavailability in erectile tissue due to eNOS/nNOS dowregulation and NOX2 upregulation, as well as hypercontractility of the penis. This rat model of ACF could be a useful tool to evaluate the molecular alterations of ED associated with HF.http://europepmc.org/articles/PMC5667775?pdf=render |
| spellingShingle | Fábio Henrique Silva Frederico José Reis Veiga Aline Gonçalves Mora Rodrigo Sader Heck Caroline Candida De Oliveira Alessandra Gambero Carla Fernanda Franco-Penteado Edson Antunes Jason D Gardner Fernanda Bruschi Marinho Priviero Mário Angelo Claudino A novel experimental model of erectile dysfunction in rats with heart failure using volume overload. PLoS ONE |
| title | A novel experimental model of erectile dysfunction in rats with heart failure using volume overload. |
| title_full | A novel experimental model of erectile dysfunction in rats with heart failure using volume overload. |
| title_fullStr | A novel experimental model of erectile dysfunction in rats with heart failure using volume overload. |
| title_full_unstemmed | A novel experimental model of erectile dysfunction in rats with heart failure using volume overload. |
| title_short | A novel experimental model of erectile dysfunction in rats with heart failure using volume overload. |
| title_sort | novel experimental model of erectile dysfunction in rats with heart failure using volume overload |
| url | http://europepmc.org/articles/PMC5667775?pdf=render |
| work_keys_str_mv | AT fabiohenriquesilva anovelexperimentalmodeloferectiledysfunctioninratswithheartfailureusingvolumeoverload AT fredericojosereisveiga anovelexperimentalmodeloferectiledysfunctioninratswithheartfailureusingvolumeoverload AT alinegoncalvesmora anovelexperimentalmodeloferectiledysfunctioninratswithheartfailureusingvolumeoverload AT rodrigosaderheck anovelexperimentalmodeloferectiledysfunctioninratswithheartfailureusingvolumeoverload AT carolinecandidadeoliveira anovelexperimentalmodeloferectiledysfunctioninratswithheartfailureusingvolumeoverload AT alessandragambero anovelexperimentalmodeloferectiledysfunctioninratswithheartfailureusingvolumeoverload AT carlafernandafrancopenteado anovelexperimentalmodeloferectiledysfunctioninratswithheartfailureusingvolumeoverload AT edsonantunes anovelexperimentalmodeloferectiledysfunctioninratswithheartfailureusingvolumeoverload AT jasondgardner anovelexperimentalmodeloferectiledysfunctioninratswithheartfailureusingvolumeoverload AT fernandabruschimarinhopriviero anovelexperimentalmodeloferectiledysfunctioninratswithheartfailureusingvolumeoverload AT marioangeloclaudino anovelexperimentalmodeloferectiledysfunctioninratswithheartfailureusingvolumeoverload AT fabiohenriquesilva novelexperimentalmodeloferectiledysfunctioninratswithheartfailureusingvolumeoverload AT fredericojosereisveiga novelexperimentalmodeloferectiledysfunctioninratswithheartfailureusingvolumeoverload AT alinegoncalvesmora novelexperimentalmodeloferectiledysfunctioninratswithheartfailureusingvolumeoverload AT rodrigosaderheck novelexperimentalmodeloferectiledysfunctioninratswithheartfailureusingvolumeoverload AT carolinecandidadeoliveira novelexperimentalmodeloferectiledysfunctioninratswithheartfailureusingvolumeoverload AT alessandragambero novelexperimentalmodeloferectiledysfunctioninratswithheartfailureusingvolumeoverload AT carlafernandafrancopenteado novelexperimentalmodeloferectiledysfunctioninratswithheartfailureusingvolumeoverload AT edsonantunes novelexperimentalmodeloferectiledysfunctioninratswithheartfailureusingvolumeoverload AT jasondgardner novelexperimentalmodeloferectiledysfunctioninratswithheartfailureusingvolumeoverload AT fernandabruschimarinhopriviero novelexperimentalmodeloferectiledysfunctioninratswithheartfailureusingvolumeoverload AT marioangeloclaudino novelexperimentalmodeloferectiledysfunctioninratswithheartfailureusingvolumeoverload |