Low frequency neuromuscular electrical stimulation applied to the bulbospongiosus muscle prolongs the ejaculation latency in a rat model

© 2023, The Author(s), under exclusive licence to Springer Nature Limited.Premature ejaculation (PE) is common, but its true pathophysiology is not clear, and treatments are limited. We aimed to investigate the effect of neuromuscular electrical stimulation applied in different modes and frequencies to the bulbospongiosus muscle on ejaculation parameters. In this study, 24 male Wistar albino rats were used. The rats were equally divided into three groups: control, high-frequency burst (HFB) and low-frequency (LF) (n = 8 each). Neuromuscular electrical stimulation was applied to the rats for 30 min. In the HFB group, this stimulation was applied in the burst mode at 80 Hz frequency using 200 microseconds (µs) transition time. In the LF group, manual stimulation was applied using a 2 Hz frequency and 200 µs transition time. Following the intraperitoneal administration of para-chloroamphetamine at a dose of 5 mg/kg, ejaculation time, increase in basal seminal vesicle pressure, seminal vesicle maximum pressure, number and interval time of seminal vesicle contractions and bulbospongiosus muscle electromyography activities were evaluated over 30 min. There was a significant difference between the groups in terms of ejaculation time (p = 0.002). The ejaculation times of the LF, HFB and control groups were 1344.71 ± 105.9, 908 ± 62 and 672 ± 149.7 s, respectively. The post hoc analysis revealed that the ejaculation time of the LF group was significantly longer than that of the HFB and control groups (p = 0.033 and p = 0.001, respectively). The remaining parameters did not differ significantly between the groups. The results showed that low-frequency (2 Hz) electrical stimulation applied to the male rats significantly prolonged the ejaculation time. It is thus considered that applying neuromuscular electrical stimulation before planned sexual activity can prevent the rhythmic contractions necessary for completing the ejaculatory process by maintaining subtetanic continuous contraction and prolonging the ejaculation time in patients with premature ejaculation complaints

Effects of the dopamine D-3 receptor agonist 7-hydroxy-2-(di-N-propylamino) tetralin in hyperthyroidism-induced premature ejaculation rat model

Various factors are involved in the aetiology of premature ejaculation (PE). Hyperthyroidism is one of the causes of acquired PE, but the exact mechanism by which it causes the disorder is not yet understood. The aim of this study was to evaluate the role of the dopaminergic system in hyperthyroidism-induced PE by the intracerebroventricular microinjection of the preferentially active dopamine receptor agonist 7-hydroxy-2-(di-N-propylamino) tetralin (7-OH-DPAT) in a rat model of this disorder. Wistar rats were randomly divided into hyperthyroid and control groups, and ejaculation was induced by the ICV administration of 7-OH-DPAT. To evaluate the emission and expulsion phases of ejaculation, measurements of seminal vesicle pressure (SVP) and electromyographic recordings of the bulbospongiosus muscle were taken. The interval between the 7-OH-DPAT administration and the first ejaculation was significantly less in the hyperthyroid group (p<.01) than in the control group, and the maximum amplitude of the SVP values revealed a statistically significant difference between the groups (p<.01). The intervals between contractions of the seminal vesicle and bulbospongiosus muscles were also significantly less in the hyperthyroid group (p=.0187) than in the control group. No other results differed significantly between the groups. This study determined that hyperthyroidism altered only the emission phase of ejaculation

Bilateral orchiectomy deteriorates the structure and function of seminal vesicles in a rat model

© 2023, The Author(s), under exclusive licence to Springer Nature Limited.The effects of hormone levels on ejaculation are known. In addition to thyroid hormone levels, testosterone levels are also associated with ejaculation, but no consensus has been reached on this issue. Thus, we investigated the effect of decreased testosterone levels due to bilateral orchiectomy on the chemical stimulation-induced ejaculation phases in rats. Twenty-one male Wistar rats were randomized into the orchiectomy, sham, and control groups, with seven rats in each group. Bilateral orchiectomy was performed. The ejaculation parameters were evaluated 5 days after the sham and bilateral orchiectomy operations and the waiting period in the control group. The seminal vesicle (SV) phasic contraction number and increase in basal pressure amplitude were significantly lower in the orchiectomy group (6.9 ± 3.3 and 0.6 ± 0.3 mmHg) than in the sham and control groups (11.2 ± 1.7 and 1.0 ± 0.4 mmHg, and 14.5 ± 6.6 and 1.1 ± 0.2 mmHg, respectively; p = 0.016 and p = 0.03, respectively). The interval between the SV contractions was significantly longer in the orchiectomy group (166.2 ± 104.3 s) than in the sham and control groups (76.0 ± 15.5 s and 63.1 ± 31.1 s, respectively; p = 0.014 (between groups), orchiectomy vs sham p = 0.040 and orchiectomy vs control p = 0.018). The SV weights of the rats were significantly lower in the orchiectomy group (0.14 ± 0.01 g) than in the sham and control groups (0.37 ± 0.05 g and 0.48 ± 0.03 g respectively; p < 0.0001 (between groups), orchiectomy vs sham p < 0.0001 and orchiectomy vs control p < 0.0001). The groups showed no significant differences in ejaculation time, SV basal pressure, SV maximum amplitude, and bulbospongiosus muscle contraction electromyographic activity. Our results partially clarified the relationship between decreased testosterone levels and ejaculation. Decreased testosterone levels caused statistically significant changes in SV functions and affected the ejaculation emission phase

Time-course changes of nLDL-induced erectile dysfunction.

Hyperlipidemia is an important risk factor for atherosclerosis and is frequently seen in patients with erectile dysfunction (ED). This study was designed to evaluate whether the acute effect of native low-density lipoprotein (nLDL) on intracavernosal pressure (ICP) is reversible and related to plasma asymmetrical dimethylarginine (ADMA), endogenous inhibition of endothelial nitric oxide synthase (eNOS) levels and eNOS expression in cavernous tissues. Hyperlipidemia was induced by a single dose of intravenous 4 mg kg(-1) nLDL. Experiments were performed 72 h (72H), 2 weeks (2W) and 8 weeks (8W) after nLDL injection. Endothelium-dependent relaxations, the ratio of ICP to mean arterial pressure (MAP; ICP/MAP), plasma ADMA levels and eNOS mRNA and protein levels were evaluated. The ICP/MAP ratio decreased in both the 2W and 8W groups. Endothelium-dependent relaxation responses to acetylcholine in the rat thoracic aorta were damaged in the 8W group. Plasma ADMA levels increased in the 8W group. mRNA expression of eNOS decreased in a time-dependent manner, whereas the protein expression increased. These results suggest that acute nLDL injection-induced impairments in erectile functions during an 8-week period are irreversible and might be related to an increase in ADMA levels and changes in the regulation of the eNOS/NO pathway

Pharmacological modulation of vascular ageing: a review from VascAgeNet

Vascular ageing, characterized by structural and functional changes in blood vessels of which arterial stiffness and endothelial dysfunction are key components, is associated with increased risk of cardiovascular and other age-related diseases. As the global population continues to age, understanding the underlying mechanisms and developing effective therapeutic interventions to mitigate vascular ageing becomes crucial for improving cardiovascular health outcomes. Therefore, this review provides an overview of the current knowledge on pharmacological modulation of vascular ageing, highlighting key strategies and promising therapeutic targets. Several molecular pathways have been identified as central players in vascular ageing, including oxidative stress and inflammation, the renin-angiotensin-aldosterone system, cellular senescence, macroautophagy, extracellular matrix remodelling, calcification, and gasotransmitter-related signalling. Pharmacological and dietary interventions targeting these pathways have shown potential in ameliorating age-related vascular changes. Nevertheless, the development and application of drugs targeting vascular ageing is complicated by various inherent challenges and limitations, such as certain preclinical methodological considerations, interactions with exercise training and sex/gender-related differences, which should be taken into account. Overall, pharmacological modulation of endothelial dysfunction and arterial stiffness as hallmarks of vascular ageing, holds great promise for improving cardiovascular health in the ageing population. Nonetheless, further research is needed to fully elucidate the underlying mechanisms and optimize the efficacy and safety of these interventions for clinical translation

Pharmacological modulation of vascular ageing : a review from VascAgeNet

Abstract: Vascular ageing, characterized by structural and functional changes in blood vessels of which arterial stiffness and endothelial dysfunction are key components, is associated with increased risk of cardiovascular and other age-related diseases. As the global population continues to age, understanding the underlying mechanisms and developing effective therapeutic interventions to mitigate vascular ageing becomes crucial for improving cardiovascular health outcomes. Therefore, this review provides an overview of the current knowledge on pharmacological modulation of vascular ageing, highlighting key strategies and promising therapeutic targets. Several molecular pathways have been identified as central players in vascular ageing, including oxidative stress and inflammation, the renin-angiotensin-aldosterone system, cellular senescence, macroautophagy, extracellular matrix remodelling, calcification, and gasotransmitter-related signalling. Pharmacological and dietary interventions targeting these pathways have shown potential in ameliorating age-related vascular changes. Nevertheless, the development and application of drugs targeting vascular ageing is complicated by various inherent challenges and limitations, such as certain preclinical methodological considerations, interactions with exercise training and sex/gender-related differences, which should be taken into account. Overall, pharmacological modulation of endothelial dysfunction and arterial stiffness as hallmarks of vascular ageing, holds great promise for improving cardiovascular health in the ageing population. Nonetheless, further research is needed to fully elucidate the underlying mechanisms and optimize the efficacy and safety of these interventions for clinical translation