Abstract
BackgroundPatients with heart failure (HF) display erectile dysfunction (ED). However, the pathophysiology of ED during HF remains poorly investigated.ObjectiveThis 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.MethodsMale 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.ResultsHF 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.ConclusionED 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.
Highlights
nitric oxide (NO) is well established as a mediator of penile erection
Erectile dysfunction (ED) in heart failure (HF) rats is associated with decreased NO bioavailability in erectile tissue due to endothelial NO synthase (eNOS)/ neuronal NO synthase (nNOS) dowregulation and NOX2 upregulation, as well as hypercontractility of the penis
This rat model of aortocaval fistula (ACF) could be a useful tool to evaluate the molecular alterations of ED associated with HF
Summary
During the physiological relaxation of cavernosal smooth muscle, when NO is released from nitrergic fibers /or endothelium NO diffuses into adjacent smooth muscle cells and binds to soluble guanylyl cyclase (GCs), NO intracellular physiological receptor. Stimulation of this enzyme by NO leads to the conversion of guanosine triphosphate (GTP) in the second-messenger, cyclic guanosine monophosphate (cGMP). Beyond the association of ED with vascular risk factors, the ED is a stronger predictor of all-cause death and cardiovascular events including acute myocardial infarction and heart failure (HF) in patients with cardiovascular diseases [4]. The pathophysiology of ED during HF remains poorly investigated
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