Silva Fábio Henrique, Veiga Frederico José Reis, Mora Aline Gonçalves, Heck Rodrigo Sader, De Oliveira Caroline Candida, Gambero Alessandra, Franco-Penteado Carla Fernanda, Antunes Edson, Gardner Jason D, Priviero Fernanda Bruschi Marinho, Claudino Mário Angelo
Hematology and Hemotherapy Center, University of Campinas, Faculty of Medical Sciences, University of Campinas, Campinas, SP, Brazil.
Laboratory of Multidisciplinary Research, São Francisco University Medical School, Bragança Paulista, SP, Brazil.
PLoS One. 2017 Nov 2;12(11):e0187083. doi: 10.1371/journal.pone.0187083. eCollection 2017.
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.
心力衰竭（HF）患者存在勃起功能障碍（ED）。然而，HF期间ED的病理生理学仍研究不足。
本研究旨在将与HF相关的主动脉腔静脉瘘（ACF）大鼠模型表征为ED的新型实验模型。我们进行了分子和功能研究，以评估阴茎中一氧化氮（NO）途径、自主神经系统和氧化应激的改变。
雄性大鼠接受ACF诱导HF。评估麻醉大鼠的海绵体内压。在假手术组和HF大鼠的海绵体平滑肌（CSM）条上获得对收缩剂（去氧肾上腺素）和松弛剂（硝普钠；SNP）以及电场刺激（EFS）的浓度-反应曲线。评估CSM中内皮型一氧化氮合酶（eNOS）、神经元型一氧化氮合酶（nNOS）和磷酸二酯酶-5的蛋白表达，以及NOX2（gp91phox）和超氧化物歧化酶（SOD）mRNA表达。还检测了血浆中的SOD活性和硫代巴比妥酸反应性物质（TBARs）。
与假手术组大鼠相比，HF大鼠表现出勃起功能障碍，表现为海绵体内压反应降低。HF组CSM中EFS引起的神经源性收缩反应更大。同样，去氧肾上腺素诱导的HF大鼠CSM收缩更大。EFS诱导的海绵体组织中的一氧化氮能反应降低，同时eNOS、nNOS和磷酸二酯酶-5蛋白表达降低。检测到HF组CSM中NOX2和SOD mRNA表达增加以及血浆TBARs增加。HF大鼠血浆SOD活性降低。
HF大鼠的ED与勃起组织中NO生物利用度降低有关，这是由于eNOS/nNOS下调和NOX2上调以及阴茎的过度收缩。这种ACF大鼠模型可能是评估与HF相关的ED分子改变的有用工具。
