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Corpus Cavernosum (corpus + cavernosum)
Kinds of Corpus Cavernosum Terms modified by Corpus Cavernosum Selected AbstractsCORPUS CAVERNOSUM AS AN ALTERNATIVE MEANS OF INTRAVENOUS ACCESS IN THE EMERGENCY SETTINGANZ JOURNAL OF SURGERY, Issue 7 2000D. Nicol Background: The present study was designed to investigate the feasibility of using the corpus cavernosum as an alternative means of intravenous access in the emergency setting. Methods: The feasibility of achieving the infusion flow rates was first ascertained using direct intracavernous infusion of normal saline. The effect of atropine and adrenaline when given via this route was then studied. Hypovolaemic shock was then induced in dogs who were then actively resuscitated via this route using normal saline, Haemaccel and whole blood. Results: Infusion flow rates were achieved for normal saline of 32.3, 50.3 and 67.3 mL per min at 100, 200 and 300 mmHg pressure, respectively. The peak effects of atropine and adrenaline via this route were seen at approximately 1 min after injection. Resuscitation using this method was uniformly successful in all dogs via the corpus cavernosum, with all reaching or exceeding their premorbid central venous pressure (CVP), and approaching or reaching their premorbid mean arterial pressure (MAP). In comparison the control dog's CVP and MAP did not rise during the period of observation after it was bled. Conclusions: The corpus cavernosum is a practical alternative means of intravenous access in the emergency setting in the dog model. [source] Spontaneous Ca2+ Waves in Rabbit Corpus Cavernosum: Modulation by Nitric Oxide and cGMPTHE JOURNAL OF SEXUAL MEDICINE, Issue 4 2009Gerard P. Sergeant PhD ABSTRACT Introduction., Detumescent tone and subsequent relaxation by nitric oxide (NO) are essential processes that determine the erectile state of the penis. Despite this, the mechanisms involved are incompletely understood. It is often assumed that the tone is associated with a sustained high cytosolic Ca2+ level in the corpus cavernosum smooth muscle cells, however, an alternative possibility is that oscillatory Ca2+ signals regulate tone, and erection occurs as a result of inhibition of Ca2+ oscillations by NO. Aims., The aim of this study is to determine if smooth muscle cells displayed spontaneous Ca2+ oscillations and, if so, whether these were regulated by NO. Methods., Male New Zealand white rabbits were euthanized and smooth muscle cells were isolated by enzymatic dispersal for confocal imaging of intracellular Ca2+ (using fluo-4AM) and patch clamp recording of spontaneous membrane currents. Thin tissue slices were also loaded with fluo-4AM for live imaging of Ca2+. Main Outcome Measure., Cytosolic Ca2+ was measured in isolated smooth muscle cells and tissue slices. Results., Isolated rabbit corpus cavernosum smooth muscle cells developed spontaneous Ca2+ waves that spread at a mean velocity of 65 µm/s. Dual voltage clamp/confocal recordings revealed that each of the Ca2+ waves was associated with an inward current typical of the Ca2+ -activated Cl - currents developed by these cells. The waves depended on an intact sarcoplasmic reticulum Ca2+ store, as they were blocked by cyclopiazonic acid (Calbiochem, San Diego, CA, USA) and agents that interfere with ryanodine receptors and IP3 -mediated Ca2+ release. The waves were also inhibited by an NO donor (diethylamine NO; Tocris Bioscience, Bristol, Avon, UK), 3-(5-hydroxymethyl-2-furyl)-1-benzyl indazole (YC-1) (Alexis Biochemicals, Bingham, Notts, UK), 8-bromo-cyclic guanosine mono-phosphate (Tocris), and sildenafil (Viagra, Pfizer, Sandwich, Kent, UK). Regular Ca2+ oscillations were also observed in whole tissue slices where they were clearly seen to precede contraction. This activity was also markedly inhibited by sildenafil, suggesting that it was under NO regulation. Conclusions., These results provide a new basis for understanding detumescent tone in the corpus cavernosum and its inhibition by NO. Sergeant GP, Craven M, Hollywood MA, McHale NG, and Thornbury KD. Spontaneous Ca2+ waves in rabbit corpus cavernosum: Modulation by nitric oxide and cGMP. J Sex Med **;**:**,**. [source] Efficient Gene Expression System Using the RTP801 Promoter in the Corpus Cavernosum of High-Cholesterol Diet-Induced Erectile Dysfunction Rats for Gene TherapyTHE JOURNAL OF SEXUAL MEDICINE, Issue 6 2008Minhyung Lee PhD ABSTRACT Introduction., The application of gene therapy for a nonlife-threatening disease, such as erectile dysfunction (ED), requires a higher safety level and more efficacious systems for gene transfer. Aim., To establish a novel technique for gene expression in a rat model of hypercholesterolemic ED that uses the RTP801 promoter, a hypoxia-inducible promoter. Methods., Two-month-old male Sprague,Dawley rats were fed a diet containing 4% cholesterol and 1% cholic acid, and age-matched control animals were fed a normal diet, for 3 months. Main Outcome Measures., Cavernous expression of hypoxia-inducible factor (HIF)-1, was evaluated by Western blot. After intracavernous injection of pSV-Luc or pRTP801-Luc, gene expression was evaluated by luciferase assay, and the gene expression area was evaluated by immunohistochemistry. Results., HIF-1, was up-regulated in the corpus cavernosum of hypercholesterolemic rats. Although pSV-Luc did not induce gene expression in either the control or the cholesterol group, pRTP801-Luc significantly induced gene expression in the cholesterol group and resulted in higher luciferase activity than did pSV-Luc up to 14 days after injection. Immunohistochemistry showed that the gene expression area was also greater in the pRTP801-Luc group than in the pSV-Luc group, but the difference was not as great as that in luciferase activity. This suggests that pRTP801-Luc exerts its effect mainly by inducing promoter activity under hypoxia, not by increasing the number of transfected cells. Conclusion., The RTP801 promoter-driven gene expression system increased gene expression in the corpus cavernosum tissue of rats with cholesterol-induced ED. This may be a useful system for the development of gene therapy in vasculogenic ED. Lee M, Ryu J-K, Piao S, Choi MJ, Kim HA, Zhang L-W, Shin H-Y, Jung HI, Kim I-H, Kim SW, and Suh J-K. Efficient gene expression system using the RTP801 promoter in the corpus cavernosum of high-cholesterol diet-induced erectile dysfunction rats for gene therapy. J Sex Med 2008;5:1355,1364. [source] CASE REPORTS: Xanthogranulomatous Inflammation of Corpus CavernosumTHE JOURNAL OF SEXUAL MEDICINE, Issue 6 2007Young Seo III MD ABSTRACT Introduction., Xanthogranulomatous inflammation is a rare, chronic destructive inflammatory lesion. The pathological finding is typically lymphocyte and plasma cell infiltration, surrounded by accumulating lipid-laden macrophages. Methods., A 65-year-old healthy man presented with a 3-week history of a painless palpable mass in the penis. Results., The patient underwent an excision of the mass with a tunica albuginea, and a graft from the tunica vaginaglis. Histopathological findings showed the diffuse xanthogranulomatous inflammation. Conclusions., Xanthogranulomatous inflammation of corpus cavernosum in old men is a rare condition. The inflammatory mass should be treated by complete excision and graft. Seo IY, Jo HJ, and Rim JS. Xanthogranulomatous inflammation of corpus cavernosum. J Sex Med 2007;4:1763,1765. [source] ORIGINAL RESEARCH,BASIC SCIENCE: A Nitric Oxide-Releasing PDE5 Inhibitor Relaxes Human Corpus Cavernosum in the Absence of Endogenous Nitric OxideTHE JOURNAL OF SEXUAL MEDICINE, Issue 1 2005Jasjit S. Kalsi BSc, MRCS ABSTRACT Introduction., In conditions with severe deficiency of endogenous nitric oxide (NO), such as long-term diabetes and cavernosal nerve injury, phosphodiesterase type 5 (PDE5) inhibitors have reduced efficacy in the treatment of erectile dysfunction. NO-releasing PDE5 inhibitors could be an alternative therapeutic approach in such cases. Aim., We therefore aimed to compare sildenafil and NO-releasing sildenafil (NCX-911) in relaxing human corpus cavernosum in the absence or presence of endogenous NO. Methods., The two compounds were compared in reducing the phenylephrine-induced tone of human corpus cavernosum in the presence or absence of an inhibitor of NO synthase (L-NAME; 500 µM) or an inhibitor of soluble guanylate cyclase (ODQ, 10 µM). Results., NCX-911 was as potent as sildenafil in control conditions (EC50 = 733.1 ± 94.4 nM and 800.7 ± 155.8 nM, respectively). The potency of NCX-911 was not altered but that of sildenafil decreased significantly in the presence of L-NAME (EC50 = 980.4 ± 106.7 nM and 2446.7 ± 256.8 nM, respectively; P < 0.001 for sildenafil vs. control). Both compounds below 1 µM failed to induce relaxation in the presence of ODQ (EC50 = 6578 ± 1150 nM and 6488 ± 938 nM for NCX-911 and sildenafil, respectively). Conclusion., These results show that the potency of NCX-911 was maintained unlike sildenafil in the absence of endogenous NO confirming the potential use of NO-releasing PDE5 inhibitors in NO-deficient conditions. [source] Xanthine-analog, KMUP-2, enhances cyclic GMP and K+ channel activities in rabbit aorta and corpus cavernosum with associated penile erectionDRUG DEVELOPMENT RESEARCH, Issue 3 2002Rong-Jyh Lin Abstract The pharmacological properties of KMUP-2 were examined in isolated rabbit aorta and corpus cavernosum smooth muscle (CCSM). KMUP-2 caused relaxations that were attenuated by removed endothelium, high K+, and pretreatment with the soluble guanylate cyclase (sGC) inhibitors methylene blue (10 ,M) and ODQ (1 ,M), a NOS inhibitor, L-NAME (100 ,M), a K+ channel blocker TEA (10 mM), a KATP channel blocker glibenclamide (1 ,M), a voltage-dependent K+ channel blocker 4-AP (100 ,M), and the Ca2+ -dependent K+ channel blockers apamin (1 ,M) and charybdotoxin (ChTX, 0.1 ,M). The relaxant responses of KMUP-2 (0.01, 0.05, 0.1 ,M) together with a PDE inhibitor, IBMX (0.5 ,M), had additive effects on rabbit aorta and CCSM. Additionally, KMUP-2 (100 ,M) also affected cGMP metabolism, due to its inhibiting activity on PDE in human platelets. KMUP-2 (0.1,100 ,M) further induced an increase of intracellular cGMP levels in the primary cultured rabbit aortic and CCSM cells. These increases in cGMP content were abolished in the presence of methylene blue (100 ,M) and ODQ (10 ,M). Obviously, the relaxant effects of KMUP-2 on rabbit isolated tissues are more sensitive in CCSM than in aorta. Moreover, KMUP-2 also stimulated NO/sGC/cGMP pathway and subsequent elevation of cGMP by blockade of PDE and enhanced opening of K+ channels in rabbit aorta and CCSM. KMUP-2 (0.2, 0.4, 0.6 mg/kg), similar to KMUP-1 and sildenafil, caused increases of intracavernous pressure (ICP) and duration of tumescene (DT) in a dose-dependent manner. It is concluded that both the increases of cGMP and the opening activity of K+ channels play prominent roles in KMUP-2-induced aortic smooth muscle and CCSM relaxation and increases of ICP in rabbits. Drug Dev. Res. 55:162,172, 2002. © 2002 Wiley-Liss, Inc. [source] Phentolamine mesylate relaxes rabbit corpus cavernosum by a nonadrenergic, noncholinergic mechanismFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 1 2001Subbarao Vemulapalli The contribution of NO-cGMP dependent pathway to phentolamine mesylate-evoked nonadrenergic, noncholinergic relaxation of rabbit corpus cavernosum was investigated in vitro. Stimulation of nonadrenergic, noncholinergic neurons of the rabbit corpus cavernosum elicited frequency-related relaxation that was significantly attenuated by L-NAME (NO synthase inhibitor) or ODQ (an inhibitor of guanylate cyclase). Moreover, tetrodotoxin, a sodium channel blocker, abolished the electrical field stimulation-induced relaxation of rabbit corpus cavernosum, suggesting that neuronal release of NO mediates relaxation to electrical field stimulation. Phentolamine mesylate (30 and 100 nM) dose-dependently enhanced electrical field stimulation-induced relaxation of the rabbit corpus cavernosum. Prazosin (30 ,M) and yohimbine (30 ,M) failed to affect phentolamine mesylate-mediated nonadrenergic, noncholinergic rabbit penile smooth muscle relaxation, suggesting that phentolamine relaxes rabbit corpus cavernosum independent of ,-adrenergic receptor blockade. In contrast, pretreatment of the rabbit cavernosal strips with L-NAME significantly-attenuated electrical field stimulation produced relaxations to phentolamine mesylate, suggesting that phentolamine mesylate relaxes rabbit corpus cavernosum by activating NO synthase. The data suggest that phentolamine mesylate relaxes nonadrenergic noncholinergic neurons of the rabbit corpus cavernosum by activating NO synthase and is independent of ,-adrenergic receptor blockade. [source] Effect of hypothyroidism on the nitrergic relaxant responses of corpus cavernosal smooth muscle in rabbitsINTERNATIONAL JOURNAL OF UROLOGY, Issue 1 2006BULENT SARAC Background:, The incidence of hormonal dysfunction as a cause of impotence remains controversial. However, several recent studies have reported evidence of hormonal abnormalities in 25,35% of impotent men. Hypothyroidism has been reported to occur in 6% of impotent men. Methods:, In the present study, we examined nitrergic responses in hypothyroidism in rabbit corpus cavernosum and compared them with controls. Results:, Carbachol-induced relaxation responses and electrical field stimulation (EFS)-induced frequency-dependent relaxations decreased significantly in hypothyroid rabbits. Papaverine and sodium nitroprusside (SNP)-induced relaxation responses did not change significantly in hypothyroid rabbits. The contraction responses of phenylephrine and EFS-induced frequency-dependent contractions were significantly decreased in the hypothyroid group. Conclusions:, We can speculate that the reduction of relaxant responses to EFS and carbachol in hypothyroid rabbits can depend on a decreased release of nitric oxide (NO) from nitrergic nerves and endothelium or a reduction of muscarinic receptor density. Also, decreases in contraction responses may depend on diminished adrenoceptor density. [source] The neuronal and endothelium-dependent relaxing responses of human corpus cavernosum under physiological oxygen tension last longer than previously expectedINTERNATIONAL JOURNAL OF UROLOGY, Issue 5 2004KAZUNORI KIMURA Abstract Background: Intracavernosal oxygen tension varies greatly in the process of erection. Blood extracted from the human penis demonstrates an increase from approximately 30 mmHg Po2 in the flaccid state to 100 mmHg in the erect state of the penis. In the present study, using these levels as a guide, we investigate how the NO-dependent relaxation of human corpus cavernosum changed under physiological oxygen tensions ranging from approximately 30 to 100 mmHg. Methods: Human penile tissue specimens were obtained at penile surgery with informed consent from the patients. The preparations were mounted in Krebs solution in an organ bath and the isometric tension was recorded. Krebs solutions of various oxygen tensions were prepared by bubbling 5% CO2 in N2 and O2. The NO-dependent relaxation caused by electrical field stimulation (EFS) and acetylcholine (ACh) was studied, and the amplitude and duration of relaxation evaluated. Results: The amplitude of relaxation induced by EFS was significantly decreased under physiological oxygen tension conditions (P < 0.01). The duration of the relaxant response induced by EFS and ACh was significantly prolonged in physiological oxygen tension conditions than in high oxygen tension (P < 0.01). However, there was no correlation between the duration of relaxation induced by EFS and each physiological oxygen tension level. The duration of relaxation induced by ACh was most prolonged at 60,69 mmHg oxygen tension. Conclusion: Physiologically, the effect of NO may last longer than was previously thought. In addition, it would seem that there is an optimal physiological oxygen tension for maximum ACh-induced relaxation. [source] High-flow priapism complicating ischemic priapism following iatrogenic laceration of the dorsal artery during a Winter procedureJOURNAL OF CLINICAL ULTRASOUND, Issue 1 2009Michele Bertolotto Abstract We report a case of a patient who developed high-flow priapism following a Winter procedure performed for the treatment of low-flow ischemic priapism. During the creation of bilateral cavernosal,glandular shunts, the tip of the left dorsal artery was accidentally lacerated. A fistula developed through the shunt between the torn artery and the cavernosal sinusoids of the tip of the left corpus cavernosum. Gray-scale and Doppler sonography and angiography allowed diagnosis and guided the therapeutic approach. © 2008 Wiley Periodicals, Inc. J Clin Ultrasound, 2009 [source] Melatonin ameliorates chronic renal failure-induced oxidative organ damage in ratsJOURNAL OF PINEAL RESEARCH, Issue 4 2004Göksel, ener Abstract:, Chronic renal failure (CRF) is associated with oxidative stress that promotes production of reactive oxygen species (ROS). Melatonin, the chief secretory product of the pineal gland, was recently found to be a potent free radical scavenger and antioxidant. The aim of this study was to examine the role of melatonin in protecting the aorta, heart, corpus cavernosum, lung, diaphragm, and kidney tissues against oxidative damage in a rat model of CRF, which was induced by five of six nephrectomy. Male Wistar albino rats were randomly assigned to either the CRF group or the sham-operated control group, which had received saline or melatonin (10 mg/kg, i.p.) for 4 wk. CRF was evaluated by serum blood urea nitrogen (BUN) level and creatinine measurements. Aorta and corporeal tissues were used for contractility studies, or stored along with heart, lung, diaphragm, and kidney tissues for the measurement of malondialdehyde (MDA, an index of lipid peroxidation), protein carbonylation (PC, an index for protein oxidation), and glutathione (GSH) levels (a key antioxidant). Plasma MDA, PC, and GSH levels and erythrocytic superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were studied to evaluate the changes of antioxidant status in CRF. In the CRF group, the contraction and the relaxation of aorta and corpus cavernosum samples decreased significantly compared with controls (P < 0.05,0.001). Melatonin treatment of the CRF group restored these responses. In the CRF group, there were significant increases in tissue MDA and PC levels in all tissues with marked reductions in GSH levels compared with controls (P < 0.05,0.001). In the plasma, while MDA and PC levels increased, GSH, SOD, CAT, and GSH-Px activities were reduced. Melatonin treatment reversed these effects as well. In this study, the increase in MDA and PC levels and the concomitant decrease in GSH levels of tissues and plasma and also SOD, CAT, GSH-Px activities of plasma demonstrate the role of oxidative mechanisms in CRF-induced tissue damage, and melatonin, via its free radical scavenging and antioxidant properties, ameliorates oxidative organ injury. CRF-induced dysfunction of the aorta and corpus cavernosum of rats was reversed by melatonin treatment. Thus, supplementing CRF patients with adjuvant therapy of melatonin may have some benefit. [source] Systemic and splanchnic haemodynamic effects of sildenafil in an in vivo animal model of cirrhosis support for a risk in cirrhotic patientsLIVER INTERNATIONAL, Issue 1 2004Isabelle Colle Abstract: Objectives: Sildenafil is a selective inhibitor of the cGMP-specific phosphodiesterase type V (PDE-V) in the corpus cavernosum. PDE-V is also present in the mesenteric artery. Cirrhosis is complicated by a splanchnic vasodilation attributed to a local overproduction of nitric oxide (NO). As sildenafil potentiates the effects of NO, it may further decrease mesenteric vascular tone and increase portal venous blood flow. The aim is to evaluate the effects of sildenafil on the systemic and splanchnic haemodynamics in an experimental model of cirrhosis. Methods: Secondary biliary cirrhosis was induced in male Wistar rats by common bile duct ligation (CBDL, n=8); control rats were sham-operated (sham, n=7). The mean arterial pressure (MAP), portal venous pressure (PVP) and arterial mesenteric blood flow (MBF) were measured after intramesenteric (0.01,10 mg/kg) and after intravenous (i.v.) (0.01,10 mg/kg) administration of sildenafil. Results: Baseline PVP was significantly higher in CBDL than in sham rats, whereas baseline MAP tended to be lower and MBF tended to be higher in CBDL compared with sham rats. Both intramesenteric and i.v. injection of sildenafil significantly decreased MAP and increased MBF and PVP in a dose-dependent way. The decrease in MAP was significantly less important in CBDL than in sham rats. The increase in MBF was importantly lower in CBDL than in sham rats. PVP tended to increase more significantly in sham rats than in CBDL. Conclusion: Sildenafil increases MBF and PVP and induces systemic hypotension. The effects are less pronounced in cirrhosis, suggesting vascular hyporesponsiveness to sildenafil. Although the rise in PVP in cirrhotic animals is smaller than in controls, it may present a risk for haemorrhagic complications. Further studies are necessary before prescribing sildenafil to patients with cirrhosis. [source] Nebivolol Dilates Human Penile Arteries and Reverses Erectile Dysfunction in Diabetic Rats through Enhancement of Nitric Oxide SignalingTHE JOURNAL OF SEXUAL MEDICINE, Issue 8 2010Javier Angulo PhD ABSTRACT Introduction., Traditional beta-blockers have sometimes been associated with erectile dysfunction (ED). Nebivolol is a cardioselective ,1 -adrenoceptor antagonist that promotes vasodilation through a nitric oxide (NO)-dependent mechanism. Aim., We evaluated the effects of nebivolol on the NO/cyclic guanosine monophosphate (cGMP) signaling pathway, on erectile function and dysfunction, and in human penile vascular tissues. Methods., Erectile response to cavernosal nerve electrical stimulation in control and diabetes-induced ED rats were evaluated, along with serum nitrite/nitrate (NOx) concentration and plasma/tissue cGMP levels. Endothelium-dependent and sildenafil-induced relaxation of isolated human corpus cavernosum (HCC) and human penile resistance arteries (HPRA) were also determined. Main Outcome Measures., The effects of nebivolol on erectile function and dysfunction and on NO/cGMP-mediated responses. Results., Treatment with nebivolol significantly potentiated erectile response in control rats, regardless of its effects on blood pressure. Nebivolol increased NOx and plasma cGMP by 3-fold and 2.75-fold, respectively, and significantly augmented the elevation of plasma cGMP produced by sildenafil. Nebivolol enhanced endothelium-dependent and sildenafil-induced relaxations of HCC tissue, and produced endothelium-dependent vasodilation of HPRA. Nebivolol, but not atenolol, significantly improved erectile response in diabetic rats (51.6%, 53.2%, and 87.1% of response at 3 Hz in nondiabetic rats, for vehicle-treated, atenolol-treated, and nebivolol-treated diabetic rats, respectively); after sildenafil administration, ED was completely reversed in nebivolol-treated diabetic rats (69.6% and 112% for diabetic rats treated with sildenafil and nebivolol plus sildenafil, respectively). Accordingly, nebivolol restored systemic NOx levels and cGMP content in penile tissue from these animals. Conclusions., Nebivolol in vivo activated the NO/cGMP pathway, enhanced erectile response and reversed ED in diabetic rats. Moreover, nebivolol in vitro potentiated NO/cGMP-mediated relaxation of human erectile tissues. These effects may account for the low incidence of ED in nebivolol-treated hypertensive patients. Nebivolol therefore may have utility in the treatment of ED, particularly ED associated with diabetes. Angulo J, Wright HM, Cuevas P, González-Corrochano R, Fernández A, Cuevas B, La Fuente JM, Gupta S, and de Tejada IS. Nebivolol dilates human penile arteries and reverses erectile dysfunction in diabetic rats through enhancement of nitric oxide signaling. J Sex Med 2010;7:2681,2697. [source] The Effect of Intracavernous Injection of Adipose Tissue-Derived Stem Cells on Hyperlipidemia-Associated Erectile Dysfunction in a Rat ModelTHE JOURNAL OF SEXUAL MEDICINE, Issue 4pt1 2010Yun-Ching Huang MD ABSTRACT Introduction., Hyperlipidemia has been associated with erectile dysfunction (ED) via damage to the cavernous endothelium and nerves. Adipose tissue-derived stem cells (ADSC) have been shown to differentiate into endothelial cells and secrete vasculotrophic and neurotrophic factors. Aim., To assess whether ADSC have therapeutic effects on hyperlipidemia-associated ED. Methods., Twenty-eight male rats were induced to develop hyperlipidemia with a high-fat diet (hyperlipidemic rats, HR). Ten additional male rats were fed a normal diet to serve as controls (normal rats, NR). Five months later, all rats were subjected to ADSC isolation from paragonadal fat. The cells were cultured for 1 week, labeled with 5-ethynyl-2,-deoxyuridine (EdU), and then injected autologously into the corpus cavernosum of 18 HR. The remaining 10 HR rats were injected with phosphate buffered saline (PBS). At 2 and 14 days post-transplantation, four rats in the HR + ADSC group were sacrificed for tracking of the transplanted cells. At 28 days post-transplantation, all remaining rats were analyzed for serum biochemistry, erectile function, and penile histology. Main Outcome Measures., Erectile function was assessed by intracavernous pressure (ICP) measurement during electrostimulation of the cavernous nerve. Cavernous nerves, endothelium, and smooth muscle were assessed by immunohistochemistry. Results., Serum total cholesterol and low-density lipoprotein levels were significantly higher in HR than in NR. High-density lipoprotein level was significantly lower in HR than in NR. Mean ICP/mean arterial pressure ratio was significantly lower in HR + PBS than in NR + PBS or HR + ADSC. Neuronal nitric oxide synthase (nNOS)-positive nerve fibers and endothelial cells were fewer in HR + PBS than in HR + ADSC. Smooth muscle content was significantly higher in both HR groups than in NR. Conclusions., Hyperlipidemia is associated with abnormalities in both the nerves and endothelium. Treatment with ADSC ameliorates these adverse effects and holds promise as a potential new therapy for ED. Huang Y-C, Ning H, Shindel AW, Fandel TM, Lin G, Harraz AM, Lue TF, and Lin C-S. The effect of intracavernous injection of adipose tissue-derived stem cells on hyperlipidemia-associated erectile dysfunction in a rat model. J Sex Med 2010;7:1391,1400. [source] Spontaneous Ca2+ Waves in Rabbit Corpus Cavernosum: Modulation by Nitric Oxide and cGMPTHE JOURNAL OF SEXUAL MEDICINE, Issue 4 2009Gerard P. Sergeant PhD ABSTRACT Introduction., Detumescent tone and subsequent relaxation by nitric oxide (NO) are essential processes that determine the erectile state of the penis. Despite this, the mechanisms involved are incompletely understood. It is often assumed that the tone is associated with a sustained high cytosolic Ca2+ level in the corpus cavernosum smooth muscle cells, however, an alternative possibility is that oscillatory Ca2+ signals regulate tone, and erection occurs as a result of inhibition of Ca2+ oscillations by NO. Aims., The aim of this study is to determine if smooth muscle cells displayed spontaneous Ca2+ oscillations and, if so, whether these were regulated by NO. Methods., Male New Zealand white rabbits were euthanized and smooth muscle cells were isolated by enzymatic dispersal for confocal imaging of intracellular Ca2+ (using fluo-4AM) and patch clamp recording of spontaneous membrane currents. Thin tissue slices were also loaded with fluo-4AM for live imaging of Ca2+. Main Outcome Measure., Cytosolic Ca2+ was measured in isolated smooth muscle cells and tissue slices. Results., Isolated rabbit corpus cavernosum smooth muscle cells developed spontaneous Ca2+ waves that spread at a mean velocity of 65 µm/s. Dual voltage clamp/confocal recordings revealed that each of the Ca2+ waves was associated with an inward current typical of the Ca2+ -activated Cl - currents developed by these cells. The waves depended on an intact sarcoplasmic reticulum Ca2+ store, as they were blocked by cyclopiazonic acid (Calbiochem, San Diego, CA, USA) and agents that interfere with ryanodine receptors and IP3 -mediated Ca2+ release. The waves were also inhibited by an NO donor (diethylamine NO; Tocris Bioscience, Bristol, Avon, UK), 3-(5-hydroxymethyl-2-furyl)-1-benzyl indazole (YC-1) (Alexis Biochemicals, Bingham, Notts, UK), 8-bromo-cyclic guanosine mono-phosphate (Tocris), and sildenafil (Viagra, Pfizer, Sandwich, Kent, UK). Regular Ca2+ oscillations were also observed in whole tissue slices where they were clearly seen to precede contraction. This activity was also markedly inhibited by sildenafil, suggesting that it was under NO regulation. Conclusions., These results provide a new basis for understanding detumescent tone in the corpus cavernosum and its inhibition by NO. Sergeant GP, Craven M, Hollywood MA, McHale NG, and Thornbury KD. Spontaneous Ca2+ waves in rabbit corpus cavernosum: Modulation by nitric oxide and cGMP. J Sex Med **;**:**,**. [source] Effects of Natriuretic Peptides on Intracavernous Pressure and Blood Pressure in Conscious RatsTHE JOURNAL OF SEXUAL MEDICINE, Issue 10 2008Naoki Aizawa PhD ABSTRACT Introduction., Natriuretic peptides activate particulate guanylyl cyclases and have been shown to induce penile erection in rats, rabbits, and humans. Aim., We investigated the effects of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) on intracavernous pressure (ICP) and systemic blood pressure (BP) in conscious, free-moving rats. Methods., ICP and BP were measured in male Sprague,Dawley rats after catheters were inserted into the crus corpus cavernosum and carotid artery, respectively. Natriuretic peptides were given by intravenous bolus (3, 10, and 30 nmol/kg) or continuous (0.1 and 1 nmol/kg/minute) administration. Main Outcome Measures., The number of animals with increases in ICP were determined. Amplitudes and durations of ICP responses and changes in BP were also evaluated. Results., More animals had multiple transient increases of ICP in response to ANP and BNP than to CNP. The increases in ICP were transient and appeared to be an "all or none" response. ANP and BNP decreased BP more than CNP, especially with bolus administration. Conclusions., These findings show that in rats, erectile responses can be initiated by ANP, BNP, and less effectively, by CNP. ANP and BNP have a high affinity for the natriuretic peptide receptor-A, suggesting that this receptor is involved in the responses. Aizawa N, Ishizuka O, Ogawa T, Mizusawa H, Igawa Y, Nishizawa O, and Andersson K-E. Effects of natriuretic peptides on intracavernous pressure and blood pressure in conscious rats. J Sex Med 2008;5:2312,2317. [source] Investigating the Effects of High-Dose Phenylephrine in the Management of Prolonged Ischaemic PriapismTHE JOURNAL OF SEXUAL MEDICINE, Issue 9 2008Asif Muneer BSc(Hons), FRCS(Urol) ABSTRACT Introduction., Acute priapism can be managed by corporal blood aspirations and the instillation of , adrenergic agonists such as phenylephrine if patients present early. Following prolonged ischaemic priapism, this regimen is often unsuccessful, and the use of phenylephrine is limited due to systemic cardiovascular side effects. Aim., To investigate the effects of high-dose phenylephrine on human corpus cavernosal smooth muscle obtained from patients presenting with refractory ischaemic priapism. Methods., Strips of corpus cavernosum were obtained from six patients presenting with prolonged ischaemic priapism (duration 60,240 hours), where detumescence was refractory to conventional doses of phenylephrine. The smooth muscle contractile response to high doses of phenylephrine were then compared with that of normal control corpus cavernosum obtained from four patients undergoing a penectomy for penile cancer. The tissue was then analyzed using TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) to assess its viability. Main Outcome Measures., The in vitro response to high-dose phenylephrine of corpus cavernosum smooth muscle obtained from patients with refractory priapism compared with normal human corpus cavernosum. Results., Corporal blood gas analysis confirmed hypoxia (pO2 1.5,2.3 kPa), acidosis (pH 6.9,7.1), and glucopenia (0,0.3 mmol/L) in all six patients confirming the ischaemic nature of the priapism. Application of high doses of phenylephrine produced a marked muscle contraction in the control tissue, but there was no contractile response at all in any of the priapism patients. Analysis with TUNEL indicated widespread smooth muscle cell apoptosis in all the priapism tissue. Conclusions., This study has shown that patients with ischaemic priapism that fails to respond to conventional doses of an ,-agonist are unlikely to benefit from continual or high-dose phenylephrine administration, as there is usually widespread apoptosis of the cavernosal smooth muscle preventing further contraction. Muneer A, Minhas S, Freeman A, Kumar P, and Ralph DJ. Investigating the effects of high-dose phenylephrine in the management of prolonged ischaemic priapism. J Sex Med 2008;5:2152,2159. [source] Intracavernous Growth Differentiation Factor-5 Therapy Enhances the Recovery of Erectile Function in a Rat Model of Cavernous Nerve InjuryTHE JOURNAL OF SEXUAL MEDICINE, Issue 8 2008Thomas M. Fandel ABSTRACT Introduction., Neurogenic erectile dysfunction remains a serious complication in the postprostatectomy population. Effective protective and regenerative neuromodulatory strategies are needed. Aim., To determine the effect of growth differentiation factor-5 (GDF-5) on erectile function and its mechanism in a rat model of cavernous nerve (CN) injury. Main Outcome Measures., Erectile function was assessed by CN electrostimulation at 4 weeks. Penile tissues were examined by real-time polymerase chain reaction (PCR) and immunohistochemical analyses. Methods., Forty-eight male Sprague-Dawley rats were randomly divided into six equal groups: one group underwent sham operation (uninjured controls), while five groups underwent bilateral CN crush. Crush-injury groups were treated at the time of injury with intracavernous injection of a slow-release suspension of liquid microparticles containing no GDF-5 (vehicle), 0.4 µg (low concentration), 2 µg (intermediate concentration), or 10 µg GDF-5 (high concentration). One untreated group served as injured controls. Results., GDF-5 enhanced erectile recovery and significantly increased intracavernous pressure in the low and intermediate-concentration groups vs. injured controls. Low-concentration GDF-5 demonstrated the best functional preservation, as the intracavernous pressure increase in this group did not differ significantly from uninjured controls. A dose-response relationship was confirmed for the effects of GDF-5 in penile tissue. Low-concentration GDF-5 showed better preservation of the penile dorsal nerves and antiapoptotic effects in the corpus cavernosum (P < 0.05 vs. injured controls). Although high concentration GDF-5 did not confer meaningful erectile recovery, this dose was more effective at decreasing transforming growth factor-, than low-concentration GDF-5. Conclusions., Intracavernous injection of low (0.4 µg) or intermediate-concentration GDF-5 (2 µg) was effective in preserving erectile function in a rat model of neurogenic erectile dysfunction. The underlying mechanism appears to involve neuron preservation and antiapoptosis. Fandel TM, Bella AJ, Lin G, Tantiwongse K, Lin C-S, Pohl J, and Lue TF. Intracavernous growth differentiation factor-5 therapy enhances the recovery of erectile function in a rat model of cavernous nerve injury. J Sex Med 2008;5:1866,1875. [source] Insulin-Like Growth Factor-1 Restores Erectile Function in Aged Rats: Modulation the Integrity of Smooth Muscle and Nitric Oxide-Cyclic Guanosine Monophosphate Signaling ActivityTHE JOURNAL OF SEXUAL MEDICINE, Issue 6 2008Xiao-Yong Pu MD ABSTRACT Introduction., Insulin-like growth factor-1 (IGF-1) is one of the growth factors that have a wide range of biologic effects. We have confirmed that gene transfer of IGF-1 to the penis could improve erectile capacity. However, there are some limitations in gene therapies, such as toxicity or a risk of insertional mutagenesis. Protein treatment may be another choice for decreasing these risks. Aim., To investigate whether intracavernosal injection of IGF-1 protein can restore erectile function in the aging rat. Main Outcome Measures., Erectile responses, morphological changes, and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling pathways-related marker were determined. Methods., Ten young (4 months) and 30 old (24 months) Sprague-Dawley male rats were enrolled in this study. The old rats were divided into three groups: vehicle-only (N = 10), IGF-1 1 µg/kg (N = 10) and IGF-1 10 µg/kg treatment group (N = 10). After 4 and 8 weeks of single IGF-1 injection treatment, intracavernous pressure (ICP) responses with electrical stimulation to the cavernous nerve were evaluated. The percent of smooth muscle in corpus cavernosum tissue, the expression of mRNA and protein of endothelial nitric oxide synthase (eNOS) were also evaluated. The activity of nitric oxide synthase (NOS) and concentration of guanosine 3,,5,-cyclic-monophosphate (cGMP) that act upon the major NO-cGMP signaling pathways in penile tissue were also analyzed. Results., After IGF-1 treatment, the ICP responses was significantly increased as the young control group in both the IGF-1 1 µg/kg and the IGF-1 10 µg/kg group compared with the vehicle-only group at 4 and 8 weeks (P < 0.05). Masson's trichrom staining showed the percentage of cavernosal smooth muscle was increased in IGF-1 treatment group. IGF-1 increased e-NOS expression. NOS activities and cGMP concentrations were also significantly increased in IGF-1 treatment rats. Conclusions., IGF-1 improved erectile function in aged rats via restoration the integrity of smooth muscle of corpus cavernosum and modulation of NO-cGMP pathways. Pu, X-Y, Wang X-H, Gao W-C, Yang Z-H, and Li S-L. Insulin-like growth factor-1 restores erectile function in aged rats: Modulation the integrity of smooth muscle and nitric oxide-cyclic guanosine monophosphate signaling activity. J Sex Med 2008;5:1345,1354. [source] Efficient Gene Expression System Using the RTP801 Promoter in the Corpus Cavernosum of High-Cholesterol Diet-Induced Erectile Dysfunction Rats for Gene TherapyTHE JOURNAL OF SEXUAL MEDICINE, Issue 6 2008Minhyung Lee PhD ABSTRACT Introduction., The application of gene therapy for a nonlife-threatening disease, such as erectile dysfunction (ED), requires a higher safety level and more efficacious systems for gene transfer. Aim., To establish a novel technique for gene expression in a rat model of hypercholesterolemic ED that uses the RTP801 promoter, a hypoxia-inducible promoter. Methods., Two-month-old male Sprague,Dawley rats were fed a diet containing 4% cholesterol and 1% cholic acid, and age-matched control animals were fed a normal diet, for 3 months. Main Outcome Measures., Cavernous expression of hypoxia-inducible factor (HIF)-1, was evaluated by Western blot. After intracavernous injection of pSV-Luc or pRTP801-Luc, gene expression was evaluated by luciferase assay, and the gene expression area was evaluated by immunohistochemistry. Results., HIF-1, was up-regulated in the corpus cavernosum of hypercholesterolemic rats. Although pSV-Luc did not induce gene expression in either the control or the cholesterol group, pRTP801-Luc significantly induced gene expression in the cholesterol group and resulted in higher luciferase activity than did pSV-Luc up to 14 days after injection. Immunohistochemistry showed that the gene expression area was also greater in the pRTP801-Luc group than in the pSV-Luc group, but the difference was not as great as that in luciferase activity. This suggests that pRTP801-Luc exerts its effect mainly by inducing promoter activity under hypoxia, not by increasing the number of transfected cells. Conclusion., The RTP801 promoter-driven gene expression system increased gene expression in the corpus cavernosum tissue of rats with cholesterol-induced ED. This may be a useful system for the development of gene therapy in vasculogenic ED. Lee M, Ryu J-K, Piao S, Choi MJ, Kim HA, Zhang L-W, Shin H-Y, Jung HI, Kim I-H, Kim SW, and Suh J-K. Efficient gene expression system using the RTP801 promoter in the corpus cavernosum of high-cholesterol diet-induced erectile dysfunction rats for gene therapy. J Sex Med 2008;5:1355,1364. [source] Expression of Messenger Ribonucleic Acid Encoding for Phosphodiesterase Isoenzymes in Human Female Genital TissuesTHE JOURNAL OF SEXUAL MEDICINE, Issue 6 2007Stefan Uckert PhD ABSTRACT Objectives., The use of inhibitors of phosphodiesterase 5 (PDE5) has been suggested to treat symptoms of female sexual dysfunction (FSD). Nonetheless, there has been a relatively low success rate of PDE5 inhibitors in FSD in comparison with male erectile dysfunction. The elevated expression of PDE5 in the human penile erectile tissue is considered the reason for the high clinical efficacy of PDE5 inhibitors in the pharmacotherapy of male erectile dysfunction. Aim., To evaluate by means of molecular biology the expression of messenger ribonucleic acid expression (mRNA) encoding for cyclic AMP and cyclic GMP PDE isoenzymes in female genital tissues. Main Outcome Measures., The amount of mRNA transcripts specifically encoding for cyclic AMP- and/or cyclic GMP-degrading PDE isoenzymes was determined. Methods., Human clitoral, labial, and vaginal tissue was obtained from four female cadavers (age at death: 18,42 years). The expression of mRNA specifically encoding for PDE1A, 1B, 1C, 2A, 4A, 5A, 10A, and 11A was elucidated by means of real-time polymerase chain reaction (PCR) analysis (TaqMan). Human penile erectile tissue (corpus cavernosum [HCC]) was used as a reference tissue. Results., mRNA encoding for all PDE isoforms mentioned above is expressed in the female genital tissues. Different magnitudes of mRNA expression were observed: a predominant expression of mRNA encoding for PDE1A but only insignificant amounts of PDE1B, 1C, 4A, 10, and 11A mRNA were registered. With PDE1A being the only exception, the mRNA expression was always higher in the HCC than in the female genital tissues. Especially, the expression of mRNA encoding for PDE5 was several-fold higher in the HCC. Conclusion., On the mRNA level, various PDE isoforms are expressed in the clitoris, labia, and vagina. It remains to be established as to whether the low expression of PDE5 in female genital tissue might be a negative predictor for the success of PDE5 inhibitors in the treatment of FSD. Uckert S, Ellinghaus P, Albrecht K, Jonas U, and Oelke M. Expression of messenger ribonucleic acid encoding for phosphodiesterase isoenzymes in human female genital tissues. J Sex Med 2007;4:1604,1609. [source] CASE REPORTS: Xanthogranulomatous Inflammation of Corpus CavernosumTHE JOURNAL OF SEXUAL MEDICINE, Issue 6 2007Young Seo III MD ABSTRACT Introduction., Xanthogranulomatous inflammation is a rare, chronic destructive inflammatory lesion. The pathological finding is typically lymphocyte and plasma cell infiltration, surrounded by accumulating lipid-laden macrophages. Methods., A 65-year-old healthy man presented with a 3-week history of a painless palpable mass in the penis. Results., The patient underwent an excision of the mass with a tunica albuginea, and a graft from the tunica vaginaglis. Histopathological findings showed the diffuse xanthogranulomatous inflammation. Conclusions., Xanthogranulomatous inflammation of corpus cavernosum in old men is a rare condition. The inflammatory mass should be treated by complete excision and graft. Seo IY, Jo HJ, and Rim JS. Xanthogranulomatous inflammation of corpus cavernosum. J Sex Med 2007;4:1763,1765. [source] ORIGINAL RESEARCH,BASIC SCIENCE: A Nitric Oxide-Releasing PDE5 Inhibitor Relaxes Human Corpus Cavernosum in the Absence of Endogenous Nitric OxideTHE JOURNAL OF SEXUAL MEDICINE, Issue 1 2005Jasjit S. Kalsi BSc, MRCS ABSTRACT Introduction., In conditions with severe deficiency of endogenous nitric oxide (NO), such as long-term diabetes and cavernosal nerve injury, phosphodiesterase type 5 (PDE5) inhibitors have reduced efficacy in the treatment of erectile dysfunction. NO-releasing PDE5 inhibitors could be an alternative therapeutic approach in such cases. Aim., We therefore aimed to compare sildenafil and NO-releasing sildenafil (NCX-911) in relaxing human corpus cavernosum in the absence or presence of endogenous NO. Methods., The two compounds were compared in reducing the phenylephrine-induced tone of human corpus cavernosum in the presence or absence of an inhibitor of NO synthase (L-NAME; 500 µM) or an inhibitor of soluble guanylate cyclase (ODQ, 10 µM). Results., NCX-911 was as potent as sildenafil in control conditions (EC50 = 733.1 ± 94.4 nM and 800.7 ± 155.8 nM, respectively). The potency of NCX-911 was not altered but that of sildenafil decreased significantly in the presence of L-NAME (EC50 = 980.4 ± 106.7 nM and 2446.7 ± 256.8 nM, respectively; P < 0.001 for sildenafil vs. control). Both compounds below 1 µM failed to induce relaxation in the presence of ODQ (EC50 = 6578 ± 1150 nM and 6488 ± 938 nM for NCX-911 and sildenafil, respectively). Conclusion., These results show that the potency of NCX-911 was maintained unlike sildenafil in the absence of endogenous NO confirming the potential use of NO-releasing PDE5 inhibitors in NO-deficient conditions. [source] Partial priapism secondary to tamsulosin: a case report and review of the literatureANDROLOGIA, Issue 3 2009M. Kilinc Summary Partial priapism is also called partial segmental thrombosis of the corpus cavernosum. It is a rare pathology, and its aetiology, physiopathology and treatment are still not completely understood. To our knowledge, partial priapism due to alpha blockers has not been reported previously in the literature. In this study, a successfully treated case of partial priapism occurring after the usage of alpha blocker is presented and discussed in light of the related literature. [source] CORPUS CAVERNOSUM AS AN ALTERNATIVE MEANS OF INTRAVENOUS ACCESS IN THE EMERGENCY SETTINGANZ JOURNAL OF SURGERY, Issue 7 2000D. Nicol Background: The present study was designed to investigate the feasibility of using the corpus cavernosum as an alternative means of intravenous access in the emergency setting. Methods: The feasibility of achieving the infusion flow rates was first ascertained using direct intracavernous infusion of normal saline. The effect of atropine and adrenaline when given via this route was then studied. Hypovolaemic shock was then induced in dogs who were then actively resuscitated via this route using normal saline, Haemaccel and whole blood. Results: Infusion flow rates were achieved for normal saline of 32.3, 50.3 and 67.3 mL per min at 100, 200 and 300 mmHg pressure, respectively. The peak effects of atropine and adrenaline via this route were seen at approximately 1 min after injection. Resuscitation using this method was uniformly successful in all dogs via the corpus cavernosum, with all reaching or exceeding their premorbid central venous pressure (CVP), and approaching or reaching their premorbid mean arterial pressure (MAP). In comparison the control dog's CVP and MAP did not rise during the period of observation after it was bled. Conclusions: The corpus cavernosum is a practical alternative means of intravenous access in the emergency setting in the dog model. [source] The investigation of putative agents, using an in vitro model, to prevent cavernosal smooth muscle dysfunction during low-flow priapismBJU INTERNATIONAL, Issue 8 2008Asif Muneer OBJECTIVE To investigate the effect of putative agents for preventing irreversible smooth muscle dysfunction, using an in vitro model of low-flow priapism (a condition conventionally managed using a combination of corporal blood aspiration and instillation of ,-adrenergic agonists), as failure of detumescence results in a high incidence of erectile dysfunction. MATERIALS AND METHODS We investigated the effects of several agents (N-acetylcysteine, BayK 8644, glutathione, digoxin, calcium and N, -nitro- l -arginine methyl ester) on the recovery of smooth muscle tone after exposure to 4 h of a combination of hypoxia, glucopenia and acidosis in corpus cavernosum isolated from rabbit. RESULTS After 4 h of ischaemia, none of the agents were able to prevent irreversible smooth muscle dysfunction. CONCLUSION Prolonged low-flow priapism leads to smooth muscle dysfunction and fibrosis within the corpus cavernosum. When ,-adrenergic agents fail to reverse the condition, surgical intervention is required. We showed that the administration of novel agents, including antioxidants, does not prevent smooth muscle dysfunction. [source] Anandamide improves the impaired nitric oxide-mediated neurogenic relaxation of the corpus cavernosum in diabetic rats: involvement of cannabinoid CB1 and vanilloid VR1 receptorsBJU INTERNATIONAL, Issue 6 2007Mehdi Ghasemi OBJECTIVE To investigate the ability of acute administration of the endogenous cannabinoid, anandamide, in vitro to alter the nonadrenegic noncholinergic (NANC)-mediated relaxation of corpus cavernosum (CC) in diabetic rats and the possible role of nitric oxide (NO), as it is well known that erectile dysfunction (ED) affects 35,75% of men with diabetes mellitus and several studies have been conducted to find appropriate strategies for treating diabetes-induced ED. MATERIALS AND METHODS Diabetes was induced in rats by streptozotocin administration and was maintained for 8 weeks. The CC were removed and isolated in organ baths for pharmacological studies. Agonist-evoked or electrical-field stimulation (EFS)-evoked smooth muscle tensions in CC strips from control and diabetic rats were measured. RESULTS The neurogenic relaxation of phenylephrine (7.5 µm)-precontracted isolated CC strips was impaired in diabetic rats. Anandamide (0.3, 1 and 3 µm) enhanced the relaxant responses to EFS in diabetic CC strips in a dose-dependent manner. This effect was antagonized by the selective cannabinoid CB1 receptor antagonist AM251 (1 µm) and the selective vanilloid receptor antagonist capsazepine (3 µm). Concurrent administration of partially effective doses of l -arginine (10 µm) and anandamide (0.3 µm) exerted a synergistic improvement in EFS-induced relaxation of diabetic CC strips (P < 0.001). The relaxant responses to the NO donor, sodium nitroprusside, were similar between diabetic and control groups. CONCLUSION For the first time, we show that acute administration of anandamide, an endogenous cannabinoid, alone or combined with l -arginine can improve nitrergic nerve-mediated relaxation of the CC in diabetic rats. This effect was mediated by cannabinoid CB1 and vanilloid VR1 receptors within the CC. [source] In vitro viability of human cavernosal endothelial and fibroblastic cells after exposure to papaverine/phentolamine and prostaglandin E1BJU INTERNATIONAL, Issue 9 2005Adrian Pilatz OBJECTIVE To investigate the influence of commercially available vasoactive drugs on human cavernosal endothelial and fibroblastic cells in vitro, as although corporal fibrosis is a well known side-effect of intracavernosal injection therapy for erectile dysfunction, the possible detrimental effect of these agents on the endothelium lining the cavernosal vascular spaces is uncertain. MATERIALS AND METHODS Cultured primary endothelial (13) and fibroblastic cells (12), obtained from potent patients undergoing penile surgery, were exposed to different physiological dilutions of prostaglandin E1 (PGE1), papaverine/phentolamine or the respective triple-mix of these agents for 30 min. Viable cells were counted and cell metabolic activity measured in these cultures 48 h after drug exposure. RESULTS There was a significant dose-dependent decrease in the viable cell count after exposure to papaverine-containing formulations, probably because of the low pH of this substance. This cytotoxic effect was more pronounced in endothelial than in fibroblastic cells, and was not apparent in the PGE1 groups. The relative increase in cell metabolic activity in cultures affected by a moderate cytotoxic effect indicated a regenerative process. CONCLUSION These comparative results in endothelial and fibroblastic cell cultures suggest that the endothelium rather than the interstitium of the corpus cavernosum is more sensitive to side-effects produced by intracavernosal injection therapy with papaverine. Thus, unfavourable consequences on the function of the endothelial layer might be as important as the risk of interstitial fibrosis. As these effects were not detected for PGE1 this drug should be preferred to papaverine in clinical practice. [source] Effect of chronic renal failure on the purinergic responses of corpus cavernosal smooth muscle in rabbitsBJU INTERNATIONAL, Issue 6 2002H. Kilicarslan Objective ,To examine purinergic relaxation responses in chronic renal failure (CRF) in an experimental rabbit model, and thus evaluate the possible involvement of the purinergic system in erectile dysfunction with CRF. Materials and methods ,The relaxant effects of ATP were measured in strips of corpus cavernosum smooth muscle taken from control and CRF rabbits. CRF was induced in New Zealand white rabbits as previously described. Penises were excised from CRF rabbits 4 weeks after inducing uraemia. In an organ bath the strips from controls and CRF rabbit corpus cavernosum were pre-contracted with phenylephrine and increasing doses of adenosine and ATP added. Results ,In the pre-contracted rabbit cavernosal tissue the relaxations induced by adenosine and ATP were unchanged in CRF. Conclusion ,The lack of any relaxant effect of adenosine or ATP on the relaxation of cavernosal smooth muscle in rabbits with CRF might be because the relaxant effects of these agents are endothelium-independent and the endothelial purinergic receptor density was unchanged in CRF. [source] Calcium dobesilate potentiates endothelium-derived hyperpolarizing factor-mediated relaxation of human penile resistance arteriesBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2003Javier Angulo We have evaluated the participation of endothelium-derived hyperpolarizing factor (EDHF) in the endothelium-dependent relaxation of isolated human penile resistance arteries (HPRA) and human corpus cavernosum (HCC) strips. In addition, the effect of the angioprotective agent, calcium dobesilate (DOBE), on the endothelium-dependent relaxation of these tissues was investigated. Combined inhibition of nitric oxide synthase (NOS) and cyclooxygenase (COX) nearly abolished the endothelium-dependent relaxation to acetylcholine (ACh) in HCC, while 60% relaxation of HPRA was observed under these conditions. Endothelium-dependent relaxation of HPRA resistant to NOS and COX inhibition was prevented by raising the extracellular concentration of K+ (35 mM) or by blocking Ca2+ -activated K+ channels, with apamin (APA; 100 nM) and charybdotoxin (CTX; 100 nM), suggesting the involvement of EDHF in these responses. Endothelium-dependent relaxation to ACh was markedly enhanced by DOBE (10 ,M) in HPRA but not in HCC. The potentiating effects of DOBE on ACh-induced responses in HPRA, remained after NOS and COX inhibition, were reduced by inhibition of cytochrome P450 oxygenase with miconazole (0.3 mM) and were abolished by high K+ or a combination of APA and CTX. In vivo, DOBE (10 mg kg,1 i.v.) significantly potentiated the erectile responses to cavernosal nerve stimulation in male rats. EDHF plays an important role in the endothelium-dependent relaxation of HPRA but not in HCC. DOBE significantly improves endothelium-dependent relaxation of HPRA mediated by EDHF and potentiates erectile responses in vivo. Thus, EDHF becomes a new therapeutic target for the treatment of erectile dysfunction (ED) and DOBE could be considered a candidate for oral therapy for ED. British Journal of Pharmacology (2003) 139, 854,862. doi:10.1038/sj.bjp.0705293 [source] | ||||||||||||||||||||||