Corpus cavernosum and rho kinase

BACKGROUND: Exchange proteins activated by cAMP 1 ( EPAC1 ) can promote vasodilatation by regulating endothelial nitric oxide synthase (eNOS) activity through the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway and prevent vascular smooth muscle contraction by restraining the ras homolog gene family, member A/Rho-associated coiled-coil forming protein kinase (RhoA/ROCK) pathway. However, the relationship among EPAC1 , androgen and erectile function is still unknown. Therefore, we attempted to investigate whether EPAC1 expresses in penile corpus cavernosum of rats and how EPAC1 affects erectile function under low androgenic conditions...

Pharmacological therapy of diabetes mellitus-induced erectile dysfunction (DMED) is intractable owig to the poor response to phosphodiesterase type 5 inhibitors (PDE5i). The surge in the number of diabetic patients makes it extremely urgent to find a novel therapy for DMED. Ferroptosis is a recently discovered form of cell death evoked by lipid peroxidation and is related to several diabetic complications. GPX4, an important phospholipid hydroperoxidase, can alleviate ferroptosis and maintain redox balance via reducing lipid peroxides...

The LIM kinases (LIMK1 and LIMK2), known as downstream effectors, and the Rho-associated protein kinase (ROCK), a regulator of actin dynamics, have effects on a diverse set of cellular functions. The LIM kinases are involved in the function of the male urogenital system by smooth muscle contraction via phosphorylation of cofilin and subsequent actin cytoskeleton reorganization. Although LIMK1 and LIMK2 share sequence similarities as serine protein kinases, different tissue distribution patterns and distinct localization during cell cycle progression suggest other biological functions for each kinase...

Stress is a risk factor for erectile dysfunction (ED); however, the pathology of stress-induced ED remains unclear. Accordingly, in this study, we investigated the mechanisms of stress-induced ED using a rat model. Ten-week-old male Wistar/ST rats were maintained in a cage filled with water to a height of 2 cm (stress group) or a normal cage (control group). We found that water immersion stress significantly enhanced the contractile response to noradrenaline in the corpus cavernosum (CC) (p < 0.05). Moreover, stress significantly decreased erectile function, as assessed by changes in intracavernous pressure (p < 0...

BACKGROUND: Erectile dysfunction (ED) occurs more frequently and causes a worse response to the first-line therapies in diabetics compared with nondiabetic men. Corpus cavernosum vascular dysfunction plays a pivotal role in the occurrence of diabetes mellitus ED (DMED). The aim of this study was to investigate the protective effects of glucagon-like peptide-1 (GLP-1) analog liraglutide on ED and explore the underlying mechanisms in vivo and in vitro . METHODS: Type 1 diabetes was induced in rats by streptozotocin, and the apomorphine test was for screening the DMED model in diabetic rats...

BACKGROUND: Erectile dysfunction (ED) is a common clinical condition with limited treatment options. The main aim of the present systematic review was to synthesize information on Rho-kinase as a novel therapeutic approach for the treatment of ED. METHODS: We performed a systematic literature study in PubMed, Google Scholar and Scopus. Included studies were original articles studied the role of Rho-kinase in the pathogenesis and/or new treatment approach for ED in animal models and clinical studies, published between 2014 and 2019...

The aim of our study was to investigate whether low androgen level inhibits the erectile function of rats by regulating the expression of P2X receptors. Thirty-six 8-week-old male SD rats were randomly divided into six groups: sham-operated groups (4w-sham, 8w-sham), castration groups (4w-cast, 8w-cast) and androgen replacement after castration groups (4w-cast + T, 8w-cast + T). The maximum intracavernous pressure/mean arterial pressure (ICPmax/MAP), the levels of serum testosterone (T) and nitric oxide (NO), and the expression of P2X1, P2X2, P2X3, eNOS, p-eNOS, ROCK1 and ROCK2 in the cavernous tissue of rats were determined...

OBJECTIVE: To investigate the improving effect of S1P3 silencing on the erectile function of spontaneous hypertension rats (SHR). METHODS: Five 12-week-old healthy male WKY rats were included in group A and another 15 12-week-old healthy male SHRs equally randomized into groups B1 (intracavernously injected with 20 μl S1P3 siRNA lentiviral vectors ［2 ×108TU/ml］), B2 (intracavernously injected with 20 μl GFP lentiviral vectors ［2 ×108TU/ml］), and C (control)...

BACKGROUND: Oxidative stress is a significant contributor to the poor treatment efficacy on erectile dysfunction induced by diabetes mellitus (DMED). Thus, understanding the mechanism underlying oxidative stress will aid in the identification of novel therapeutic targets. AIM: To define the role of Janus kinase 2 (JAK2) in mediating oxidative stress in the corpus cavernosum smooth muscle cells (CCSMCs) and to investigate the therapeutic effect of monomeric berberine (BB), which inhibits JAK2, in the pathogenesis of DMED...

OBJECTIVE: To investigate the relationship between the upregulated expression of sphingosine-1-phosphate receptor 1 (S1P1) in the corpus cavernosum and erectile function in spontaneously hypertensive rats (SHRs). METHODS: Twelve-week-old healthy male Wistar-Kyoto rats (WKY) and SHR rats were randomly divided into 4 groups: WKY, SHR, WKY transfection, and SHR transfection (n = 5). A lentiviral vector carrying the S1P1 gene was injected into the corpus cavernosum penis of rats in the transfection groups (1 × 109 TU/mL, 20 μL)...

In several animal and human studies, the contribution of the endothelium, nitric oxide/soluble guanosine monophosphate (NO/cGMP) pathway, adenylyl cyclase, phosphodiesterase (PDE), potassium (K+ ) channels, L-type calcium channels, Na+ -K+ -ATPase, muscarinic acetylcholine receptors, RhoA/Rho-kinase pathway, and cyclooxygenase (COX)/arachidonic acid cascade on the relaxant mechanism of L-cysteine/H2 S pathway in corpus cavernosum has been investigated. In this chapter the relaxant mechanisms of H2 S in corpus cavernosum is discussed with data available in the current relevant literature...

OBJECTIVE: The aim of this study was to investigate the effect of chronic exendin-4 (Ex-4) treatment on corpus cavernosum (CC) dysfunction in methylglyoxal (MGO) administered rats. METHODS: Male rats were divided into four groups as control, MGO (75 mg/kg/day in drinking water for 12 weeks), MGO + low-dose Ex-4 (0.1 μg/kg twice daily subcutaneously for 12 weeks concomitant with MGO), and MGO + high-dose Ex-4 (1 μg/kg twice daily subcutaneously for 12 weeks concomitant with MGO)...

BACKGROUND/AIMS: We aim to explore the role of angiotensin (Ang)II and the RhoA/Rho kinase signaling pathway in the pathogenesis of erectile dysfunction in diabetes mellitus (DM). METHODS: Male Sprague-Dawley (SD) rats were used for experiments and short hairpin RNA (shRNA) was used to silence the AngII gene. The erectile function of rats was observed and intracavernous pressure and mean arterial pressure (ICP/MAP) were measured after electrical stimulation. Relaxation and contraction of smooth muscle in the corpus cavernosum were tested...

Eupatilin (5,7-dihydroxy-3,4,6-trimethoxyflavone) is one of the main compounds present in Artemisia species. Eupatilin has both antioxidative and anti-inflammatory properties and a relaxation effect on vascular contraction regardless of endothelial function. We evaluated the relaxant effects of eupatilin on the corpus cavernosum (CC) of rabbits and the underlying mechanisms of its activity in human corpus cavernosum smooth muscle (CCSM) cells. Isolated rabbit CC strips were mounted in an organ bath system. A conventional whole-cell patch clamp technique was used to measure activation of calcium-sensitive K+ -channel currents in human CCSM cells...

BACKGROUND: Penile corpus cavernosum is an extremely vascularized tissue and cavernosal smooth muscle tone is regulated by the balance between contractile and relaxant factor. We investigated the possible role of arachidonic acid/cyclooxygenase cascade, phosphodiesterase IV (PDEIV) and Rho-kinase in exogenous hydrogen sulfide (H2 S)-induced relaxation in mouse corpus cavernosum. METHODS: The relaxant response to H2 S (NaHS as exogenous H2 S; 1-1000μM) were obtained in isolated mouse corpus cavernosum tissues which pre-contracted by phenylephrine (5μM)...

BACKGROUND/AIM: The effects of chronic ethanol consumption on male sexual function are debateable, and its effects on the Rho/Rho-kinase pathway are unknown. Therefore, we investigated smooth muscle reactivity and Rho/Rho-kinase signalling in the corpus cavernosum of ethanol-fed mice. MATERIALS AND METHODS: Ethanol was added to drinking water at 5% concentration in the first 2 days with 5% increment every subsequent 2 days, up to a final concentration of 20% for 45 days...

OBJECTIVES: To evaluate the expression of the Rho/Rho-associated protein kinase (ROCK) pathway in the corpus cavernosum of patients with severe erectile dysfunction (ED) compared with healthy human corpus cavernosum, and to test the functional effects of two Rho kinase inhibitors (RKIs) on erectile tissue of patients with severe ED, which did not respond to phosphodiesterase type 5 inhibitors (PDE5Is). PATIENTS AND METHODS: Human corpus cavernosum samples were obtained after consent from men undergoing penile prosthesis implantation (n = 7 for organ bath experiments, n = 17 for quantitative PCR [qPCR])...

Our previous studies have demonstrated that erectile function was preserved in aged transgenic rats (TGR) harboring the human tissue kallikrein 1 (hKLK1), while the molecular level of hKLK1 on corporal fibrosis to inhibit age-related erectile dysfunction (ED) is poorly understood. Male wild-type Sprague-Dawley rats (WTR) and TGR harboring the hKLK1 gene were fed to 4- or 18-month-old and divided into three groups: young WTR (yWTR) as the control, aged WTR (aWTR), and aged TGR (aTGR). Erectile function of all rats was assessed by cavernous nerve electrostimulation method...

INTRODUCTION: Human tissue kallikrein 1 (hKLK1) has enormous potential for the protection of vasodilation and endothelial function in the cardiovascular system. Our previous study proved the decreased expression of kallikrein 1 in the corpus cavernosum (CC) of aged rats, but the role of kallikrein 1 in age-related erectile dysfunction remains unknown. AIM: To explore the effect and underlying mechanisms of hKLK1 on age-related erectile dysfunction. METHODS: Male wild-type Sprague-Dawley rats (WTR) and transgenic rats harboring the hKLK1 gene (TGR) were fed to 4 and 27 months of age, respectively, and divided into four groups: young WTR (yWTR) as the control, young TGR (yTGR), aged WTR (aWTR), and aged TGR (aTGR)...

OBJECTIVE: To investigate the expression of RhoA/Rho-kinase (ROCK) in penile corpus cavernosum smooth muscles in rats of hyperlipidemia-induced erectile dysfunction and its molecular mechanism. METHODS: Forty male Sprague-Dawley rats were randomly divided into control and experimental groups using a random number table. Rats in the control group (n=20) were fed with regular diet for 24 weeks and those in the experimental group (n=20) with high-fat diet for the same period of time...