Testosterone replacement maintains smooth muscle content in the corpus cavernosum of orchiectomized rats

Objective:To evaluate the effects of testosterone(T)on the maintenance of corpus cavernosum(CC)structure and apoptosis.Methods:Animals were divided into three groups:sham operation group(n Z 8)underwent sham operation;Orchiectomized(Orchiec)t oily vehicle group(n Z 8)underwent bilateral orchiectomy and received a single dose of oily vehicle by intramuscular injection(i.m.)30 days after orchiectomy;and Orchiec t T group(n Z 8)underwent bilateral orchiectomy and received a single dose of T undecanoate 100 mg/kg i.m.30 days after the surgery.Animals were euthanized 60 days after the beginning of the experiment with an anesthetic overdose of ketamine and xylazine.Blood samples and penile tissue were collected on euthanasia.

A Rare Presentation of Partial Segmental Thrombosis of the Corpus Cavernosum Secondary to Sickle Cell Anemia

Background: Partial segmental thrombosis of the corpus cavernosum, known as partial priapism, is an uncommon urological condition which predominantly affects young men in which the proximal part of one corpus cavernosum is thrombosed. Many risk factors have been described in the literature, however, the exact etiology of penile thrombosis and its pathogenesis remains unclear. Several treatment options are available ranging from conservative medical treatment, surgical intervention, or simple follow-up observation without treatment. Aim: In this study, we describe a patient with sickle cell anemia who presented with pain and a perineal swelling that was eventually diagnosed as partial priapism utilizing MRI scan and was treated conservatively with a successful outcome. We then performed a literature search of similar cases highlighting incidence, risk factors and management of this rare presentation. Case Presentation: A 23-year-old male who is known with sickle cell anemia presented to casualty with a 1-day history of perineal pain of a sudden onset associated with perineal swelling and vomiting. Genitourinary exam findings confirmed the absence of classic priapism. Careful examination of his perineal area revealed the presence of a fixed, hard, and tender mass at the proximal part of the penis. It was not attached to the overlying skin and no enlarged pelvic lymph nodes were felt. Once stabilized, MRI of the pelvis was performed showing right intra-tunical corpus cavernosum features suggestive of hematoma in keeping with partial segmental thrombosis of the corpus cavernosum. Conservative treatment was initiated, and the patient was managed expectantly in which he improved gradually with eventual disappearance of the perineal mass. Conclusion: Partial segmental thrombosis of the corpus cavernosum is a rare urological condition. Pathogenesis and etiologies are poorly understood but risk factors have been advocated of which sickle cell anemia is one of them. MRI has a crucial role in the diagnosis under this condition. Conservative treatment appears to be a reliable initial therapeutic option.

Quantitative assessment of the aging corpus cavernosum by shear wave elastography

We wanted to determine whether shear wave elastography(SwE)could be used to evaluate the aging degree of the corpus cavernosum(CC)and to identify the histological basis of changes in SWE measurements during the aging process.We performed a crosssectional study enrolling healthy participants of different ages.We measured the Young's modulus(YM)of the penile CCs by SWE and assessed erectile function using the International Index of Erectile Function-5(IIEF-5).Histological investigation was performed in surgically resected penile specimens from a separate group of patients to examine the smooth muscle and collagen content of the CCs.Furthermore,we measured the YM,erectile function,smooth muscle,and collagen content of the CCs in different age groups of rats.Finally,we enrolled 210 male volunteers in this study.The YM of the CC(CCYM)was positively correlated with age(r=0.949,P<0.01)and negatively correlated with erectile function(r=-0.843,P<0.01).Histological examinations showed that cCs had increased collagen content but decreased smooth muscle content with increased age.The same positive correlation between CcYM and age was also observed in the animal study.In addition,the animal study showed that older rats,with increased CcYM and decreased erectile function,had lower smooth muscle content and higher collagen content.SwE can noninvasively and quantitatively evaluate the aging degree of the Cc.Increased collagen content and decreased smooth muscle content might be the histological basis for the effect of aging on the CC and the increase in its YM.

Effects of aqueous leaf extract of Tridax procumbens on contractile activity of corpus cavernosum in N-nitro-L-arginine methyl ester-induced hypertensive male rats

Objective: This study investigated the effects of aqueous leaf extract of Tridax procumbens(ALETP) on contractile activity of corpus cavernosum in N-nitro-L-arginine methyl ester(L-NAME)-induced hypertensive male rats.Methods: Twenty normal, adult male rats(130–150 g) were divided into four groups of five rats each.Group I(control) was given normal saline(0.6 m L/kg) and group II was given L-NAME(40 mg/kg) for 6 weeks. Groups III and IV also received L-NAME(40 mg/kg) for 6 weeks but were further co-treated with 100 and 200 mg/kg of ALETP, respectively, from week 4 to week 6. All treatments were given orally. Strips of corpus cavernosum from each of the four groups were exposed to increasing concentrations of acetylcholine(ACh) and sodium nitroprusside(SNP)(10^(-9)–10^(-5) mol/L) after contraction with phenylephrine(10^(-7) mol/L) to test for a dose–response effect. Response to potassium and calcium was also measured after cumulatively adding potassium and calcium(10–50 mmol/L) to potassium-and calcium-free organ chamber. Isometric contractions were recorded through an Ugo Basile data capsule acquisition system.Results: Mean arterial blood pressure was significantly reduced in the ALETP co-treated group compared to the control and L-NAME-only groups(P < 0.05). Cavernosa strips from ALETP co-treated rats exhibited significant inhibition of contraction in response to phenylephrine, potassium chloride, and calcium chloride(P < 0.05). Relaxation in response to Ach and SNP was also significantly impaired in cavernosa strips from the L-NAME-only treated group(P < 0.05), while ALETP co-treated groups showed enhanced percentage relaxation.Conclusion: ALETP treatment of L-NAME-induced hypertensive rats promotes a relaxant effect on isolated cavernosa strips. ALETP shows potential in correcting erectile dysfunction in hypertension.

Neurovascular Evaluation in Eugonadal Men with Type 2 Diabetes Mellitus and Erectile Disfunction:A Comparative Study between Responders and Not Responders to Phosphodiesterase 5 Inhibitors

The aim of our study was to evaluate functional alterations of the corpus cavernusum and its correlation with the lack of response to treatment with PDE5i in eugonadal patients with Type 2 Diabetes Mellitus and Erectile Dysfunction. In this prospective randomized study we included 157 patients. All were treated with 5 mg tadalafil daily and 100 mg sildenafil on demand and the response to treatment was assessed in 6 month by dividing them into 2 groups: G1: Good response. Significative improvement of erectile function according to IIEF-5, and G2: There was not an improvement with the treatment. At the end of the treatment we performed neurological and vascular studies to both groups. Also we performed CC-EMG in order to evaluate penile autonomic neuropathy. 82 patients were included in G1 and 75 in G2. The time evolution of the ED was 1.5 years for G1 and 5 years for G2. Average fasting glucose and glycosilated hemoglobin values were significantly higher in G2 than in G1. Also we observed significant differences in penile vascular parameters between both groups. Peripheral neuropathy parameters did not show differences between both groups. Cavernous smooth muscle electromyography showed asynchronous and asymetric potentials in G1 (minimal autonomic neuropathy) and denervation potentials in G2 characteristic of severe CC damage. It is concluded that vascular and autonomic alterations are causes of severe CC damage and lack of response to treatment with PDE5i in this population. Peripheral neuropathy is not part of this process.

The near-infrared dye IR-61 restores erectile function in a streptozotocin-induced diabetes model via mitochondrial protection

This study aimed to evaluate the therapeutic effect of IR-61,a novel mitochondrial heptamethine cyanine dye with antioxidant effects,on diabetes mellitus-induced erectile dysfunction(DMED).Eight-week-old male Sprague-Dawley rats were intraperitoneally injected with streptozotocin(STZ)to induce type 1 diabetes.Eight weeks after STZ injection,all rats were divided into three groups:the control group,DM group,and DM+IR-61 group.In the DM+IR-61 group,the rats were administered IR-61(1.6 mg kg-1)twice a week by intravenous injection.At week 13,erectile function was evaluated by determining the ratio of the maximal intracavernous pressure to mean arterial pressure,and the penises were then harvested for fluorescent imaging,transmission electron microscopy,histological examinations,and Western blot analysis.Whole-body imaging suggested that IR-61 was highly accumulated in the penis after intravenous injection.IR-61 treatment significantly improved the maximal ICP of diabetic rats.Additionally,IR-61 ameliorated diabetes-induced inflammation,apoptosis,and phenotypic transition of corpus cavernosum smooth muscle cells(CCSMCs)in penile tissue.IR-61 also attenuated mitochondrial damage,reduced reactive oxygen species production in the corpus cavernosum and upregulated sirtuinl(SIRT1),sirtuin3(SIRT3),nuclear factor(erythroid-derived 2)-like 2(Nrf2),and heme oxygenase expression in penile tissue.In conclusion,IR-61 represents a potential therapeutic option for DMED by protecting the mitochondria of CCSMCs,which may be mediated by activation of the SIRT1,SIRT3,and Nrf2 pathways.

Upregulation of the angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas receptor axis by a combination of Yinyanghuo(Herba Epimedii Brevicornus) and Cheqianzi(Semen Plantaginis) improves erectile function in spontaneously hypertensive rats

OBJECTIVE:To evaluate the effects of a combination of Yinyanghuo(Herba Epimedii Brevicornus)(HEB)and Cheqianzi(Semen Plantaginis)(SP)on erectile dysfunction caused by essential hypertension in spontaneously hypertensive rats(SHRs),and to elucidate the role of the angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas receptor(ACE2/Ang[1-7]/Mas receptor)axis in this process.METHODS:A total of 24 SHRs were randomly assigned to three groups:SHR-control,low-dose(12.5 g/kg)and high-dose(25 g/kg)HEB+SP(HEBSP).Eight Wistar-Kyoto rats were used as normal controls.HEBSP was administered by oral gavage for 28 d.Erectile function was measured once a week using the Heaton test.After 4 weeks of treatment,the corpus cavernosum was harvested from each rat to measure nitric oxide(NO),nitric oxide synthase(e NOS)and Ang(1-7)levels,as well as ACE2,Mas receptor and neuronal nitric oxide synthase(n NOS)protein expression.RESULTS:After 4 weeks of treatment,HEBSP significantly increased erectile function in the treated group compared with SHR-control group(P<0.01).Additionally,HEBSP treatment significantly increased cavernosal levels of Ang(1-7),e NOS and NO.Moreover,HEBSP significantly elevated the expression levels of ACE2,Mas receptor and n NOS.These beneficial effects were elevated in the high-dose HEBSP group.CONCLUSION:HEBSP improved erectile function in SHRs by upregulating the ACE2/Ang(1-7)/Mas receptor axis,e NOS and n NOS pathways.