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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

A novel experimental model of erectile dysfunction in rats with heart failure using volume overload

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Author(s):
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Silva, Fabio Henrique [1] ; Reis Veiga, Frederico Jose [2] ; Mora, Aline Goncalves [2] ; Heck, Rodrigo Sader [2] ; De Oliveira, Caroline Candida [2] ; Gambero, Alessandra [2] ; Franco-Penteado, Carla Fernanda [1] ; Antunes, Edson [3] ; Gardner, Jason D. [4] ; Marinho Priviero, Fernanda Bruschi [2] ; Claudino, Mario Angelo [2]
Total Authors: 11
Affiliation:
[1] Univ Estadual Campinas, Fac Med Sci, Hematol & Hemotherapy Ctr, Campinas, SP - Brazil
[2] Sao Francisco Univ, Med Sch, Lab Multidisciplinary Res, Braganca Paulista, SP - Brazil
[3] Univ Estadual Campinas, Fac Med Sci, Dept Pharmacol, Campinas, SP - Brazil
[4] Louisiana State Univ, Hlth Sci Ctr, Dept Physiol, Baton Rouge, LA 70803 - USA
Total Affiliations: 4
Document type: Journal article
Source: PLoS One; v. 12, n. 11 NOV 2 2017.
Web of Science Citations: 2
Abstract

Background Patients with heart failure (HF) display erectile dysfunction (ED). However, the pathophysiology of ED during HF remains poorly investigated. Objective 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. Methods 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 (gp91 (phox)) and superoxide dismutase (SOD) mRNA expression. SOD activity and thiobarbituric acid reactive substances (TBARs) were also performed in plasma. Results 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. Conclusion 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. (AU)

FAPESP's process: 11/21095-4 - Morphofunctional and molecular study of erectile function and lower urinary tract in rats with chronic heart failure: evaluation of the NO-sGC-cGMP signaling pathway
Grantee:Mário Angelo Claudino
Support Opportunities: Research Grants - Young Investigators Grants