Home About us Contact
|
Home About us Contact | ||
|
|
||
Human Corpus Cavernosum (human + corpus_cavernosum)
Selected AbstractsORIGINAL 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] 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] 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] 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] 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] 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] | ||||||||||