尼古丁对大鼠阴茎海绵体内源性CO浓度及NOS活性的影响

目的:观察尼古丁对成年雄性大鼠阴茎海绵体内源性一氧化碳(CO)浓度及一氧化氮合酶(NOS)活性的影响,探讨吸烟对勃起功能损害的可能机制。方法:40只成年雄性Wistar大鼠分为4组,尼古丁注射1个月组、2个月组、3个月组和对照组,尼古丁注射组尼古丁0.5 mg/(kg.d)皮下分别注射1、2、3个月,对照组注射生理盐水。处理后,取阴茎海绵体,用改良双波长分光光度法检测CO浓度,改良Griess法检测NOS活性。结果:对照组CO浓度为(13.66±0.40)μmol/mg prot,NOS活性为(9.72±0.47)U/mg prot。尼古丁注射1个月,CO浓度和NOS活性分别下降为(12.43±0.56)μmol/mg prot和(8.44±0.69)U/mg prot,显著低于对照组(P均<0.01);尼古丁注射2个月,CO浓度和NOS活性分别下降为(11.41±0.52)μmol/mg prot和(7.53±0.24)U/mg prot,显著低于对照组和尼古丁注射1个月组(P<0.01);尼古丁注射3个月,海绵体CO浓度和NOS活性分别下降为(10.52±0.59)μmol/mg prot和(6.64±0.31)U/mg prot,均显著低于对照组和尼古丁注射1个月、2个月组(P均<0.01)。结论:尼古丁可导致成年雄性大鼠阴茎海绵体内源性CO浓度及NOS活性下降,提示内源性CO及NOS参与吸烟引起勃起功能障碍的病理生理过程。     

人参皂甙对去势大鼠阴茎海绵体组织NO含量与细胞凋亡的影响

目的研究人参皂甙对去势大鼠阴茎海绵体组织细胞凋亡、NO含量的影响,探讨人参皂甙壮阳功效的可能机制。方法40只成年雄性大鼠随机分为去势组、对照组及不同剂量(25mg/kg、100mg/kg)人参皂甙组共4组,1周后取阴茎海绵体,放免法检测血清睾酮含量(ng/ml),全自动生化分析仪比色法测定海绵体NO含量(μg/g),末端脱氧核糖核酸转移酶介导的duTP缺口末端标记法测定细胞凋亡。结果对照组血清睾酮水平浓度为(1.51±0.86),在去势组、人参皂甙治疗组(25mg/kg、100/mg/kg)均未测到。去势组阴茎海绵体NO浓度(14.45±2.38)较对照组(39.8±3.28)显著降低(P<0.01),25mg/kg人参皂甙组阴茎海绵体NO水平(16.02±2.67)与去势组(14.45±2.38)接近(P>0.05),100mg/kg人参皂甙组NO水平(37.88±7.06)较去势组细胞凋亡数(14.45±2.38)明显升高(P<0.05),与对照组(39.8±3.28)接近(P>0.05)。大剂量100mg/kg人参皂甙组(12.51±1.81)较去势组(26.02±5.25)低(P<0.05)。25mg/kg人参皂甙组凋亡细胞积分光密度(27269.60±4920.42)与去势组比较(33931.50±2459.36)差异无统计学意义,大剂量100mg/kg人参皂甙组(18766.36±3040.42)较去势组(33931.54±2459.36)低,两者比较差异有统计学意义(P<0.05)。结论100mg/kg剂量的人参皂甙不能增加去势大鼠血清睾酮含量,但可以提高去势大鼠阴茎海绵体组织NO水平,减少海绵体细胞凋亡。人参皂甙对去势大鼠阴茎海绵体细胞凋亡的抑制作用可能与其增加NO水平有关。     

组织激肽释放酶对大鼠阴茎海绵体平滑肌cAMP 和cGMP影响的研究

目的探讨组织激肽释放酶对大鼠阴茎海绵体平滑肌cAMP和cGMP的影响，以初步阐明其舒张阴茎海绵体平滑肌的机制。方法采用放射免疫法，测定组织激肽释放酶对培养的大鼠阴茎海绵体平滑肌(去内皮组)和阴茎海绵体平滑肌组织(未去内皮组)cAMP和cGMP的影响，并以硝普钠为阳性对照，以赋形剂为阴性对照。结果100mu组织激肽释放酶使阴茎海绵体平滑肌组织内cAMP和cGMP浓度分别增高2．13倍和2．54倍，而对培养的阴茎海绵体平滑肌cAMP和cGMP没有明显作用。结论组织激肽释放酶能内皮依赖性地提高阴茎海绵体平滑肌细胞内cAMP和cGMP的水平，发挥舒张阴茎海绵体平滑肌的效应。     

Inhibition of sympathetic neuroeffector transmission in human corpus cavernosum

Study Type – Aetiology (case control) Level of Evidence 2b What's known on the subject? and What does the study add? In the present study the mechanisms regulating EFS‐evoked neurogenic contraction in the human corpus cavernosum (HCC) were investigated. Overall, our data adds to current knowledge that the NO‐independent heme dependent activation of sGC and the RhoA/Rho‐kinase signaling pathways play an important role in the regulation of neurogenic contractile activity in HCC tissue.

OBJECTIVE

• ? To investigate the mechanisms of adrenergically mediated smooth muscle contraction in the human corpus cavernosum (HCC) using an organ bath approach.

METHODS

• ? Human corpus cavernosum specimens were obtained from patients (aged 59–72 years) with erectile dysfunction (ED), undergoing penile prosthesis implantation surgery.
• ? Isolated HCC strips (1 × 1 × 6 mm) were suspended in tissue bath chambers for isometric tension recording.
• ? The effects of various drugs on neurogenic contractions evoked by electrical field stimulation (EFS) were investigated. The drugs included nitric oxide (NO) donors, phosphodiesterase 5 (PDE5) inhibitor, Rho kinase (ROCK) inhibitor, NO‐independent stimulator, L‐type Ca2+ channel blocker and α‐receptor antagonist.

RESULTS

• ? Pre‐incubation with the NO donor sodium nitroprusside (SNP; 10⁴ M) significantly reduced the initial peak increase in tension evoked by EFS (by 71%, P < 0.05). The PDE5 inhibitor sildenafil (10^?4 M) reduced the increase in tension by 69%, while a combination of sildenafil and ROCK inhibitor, fasudil, inhibited tension by 81%.
• ? The EFS‐induced contractile response at 80 Hz was decreased by 65% with fasudil and by 70% with isradipine (P < 0.001), while a combination of these drugs decreased the response by 88%. An NO‐independent stimulator soluble guanylate cyclase (sGC), BAY 41‐8543, significantly reduced the response (by 82%, P < 0.001) Phentolamine, an α‐receptor antagonist, nearly eliminated the contractile response (98%, P < 0.001).

CONCLUSIONS

• ? These data suggest that neurogenic contractions are mediated by an increase in Ca(2+) influx via L‐type voltage‐gated Ca(2+) channels and that an increase in Ca(2+) sensitivity is mediated by the ROCK pathway and the PDE5 enzyme system as well as by the inhibitory NO/sGC/cGMP pathway.
• ? The neurogenic contractile response in HCC is mediated by several intracellular pathways, including adrenergic receptors, Ca(2+) entry, Ca(2+) sensitization and activation of the PDE5 enzyme. The Rho‐kinase (ROCK) inhibitor fasudil, L‐type Ca(2+) channel antagonist isradipine, and PDE5 inhibitor sildenafil, as well as a NO‐independent stimulator of sGC, had similar inhibitory effects, suggesting parallel mechanisms in the HCC.

     

Comparative studies on intracellular calcium and nadh fluorescence of the rabbit corpus cavernosum

Erectile function (erection and detumescence) involves the complex interaction of direct neuronal stimulation of corporal smooth muscle, neurohumoral release of specific endothelial contractile and relaxant factors, and secondary modulation by a variety of putative neuropeptides and vasoactive modulators. Using surface spectrofluorometry, we have correlated spontaneous contractile activity and the contractile response to field and pharmacological agents with intracellular calcium and NADH metabolism. The results demonstrate that the corpus cavernosal tissue has very unusual properties. Spontaneous contractile activity is correlated with a phasic increase in intracellular calcium. However, spontaneous contractile activity is most often correlated with a bi-phasic effect on the ratio of NADH/NAD. At the start of the spontaneous contraction, there is a sharp phasic increase in NADH/NAD; peak contractile force occurs simultaneous with a phasic decrease in this ratio showing that at peak force generation, there is a decrease in the level of intracellular energy. Phenylephrine stimulation results in an increase in intracellular calcium in proportion to the increase in tension; however, phenylephrine stimulation at low concentrations results in a net increase in the NADH/NAD ratio whereas high concentrations of phenylephrine result in a net decrease in the NADH/NAD ratio. In general, field stimulation results in a decrease in tension at low frequencies, a biphasic response at midfrequencies, and a contraction at high frequencies. These contractile responses are directly related to alterations in the intracellular concentration of calcium. That is, a decrease in tension is preceded by a decrease in intracellular calcium while an increase in tension is preceded by an increase in intracellular free calcium. Field stimulation results in a rapid and phasic alteration in the NADH/NAD ratio; however, the NADH/NAD response can be either an increase, decrease, or biphasic response. There does not appear to be a consistent relationship between the contractile/relaxant response to field stimulation and altered NADH/NAD ratio. Finally, ATP, bethanechol, and nitroprusside induce a decrease in the basal tension of the corpus cavernosal strips which corresponds with a decrease in the NADH/NAD ratio. However, whereas nitroprusside relaxation is correlated with a decreased intracellular calcium level, both ATP and bethanechol stimulate an increase in intracellular free calcium. These studies indicate that the response of the corpus cavernosal tissue to both field stimulation and pharmacological agents is complex and may involve both direct and indirect actions of a variety of cellular mediators on the corporal smooth muscle. © 1994 Wiley-Liss, Inc.     

Effects of platelet-activating factor on nitrergic transmission in rabbit corpus cavernosum

AIM: The information currently available suggests that nonadrenergic noncholinergic (NANC) transmitters, particularly nitric oxide, are involved in the relaxation of penile erectile tissues. Platelet-activating factor (PAF) is a chemical mediator and is involved in many physiological and pathophysiological events. It is well known that several of the vascular actions of PAF are mediated by the generation of nitric oxide. We designed this study to test the hypothesis that PAF has an effect on NANC responses in rabbit corpus cavernosum strips. METHODS: Rabbit corpus cavernosum strips were precontracted with phenylephrine (10(-5) mol/L). Isometric tension changes produced by carbachol (10(-9)-10(-5) mol/L), sodium nitroprusside (10(-8)-10(-5) mol/L) and electrical field stimulation (for 10 s at sequential frequencies of 2, 4, 8, 16, and 32 Hz as square-wave pulses of 50 mV) were recorded with a pressure transducer. These relaxations were compared to those obtained in the presence of PAF. RESULTS: PAF had no effect on endothelium-dependent, endothelium-independent or electrical field stimulation-induced NANC relaxation responses in isolated rabbit corpus cavernosum strips. There was no statistically significant difference between the pD(2) and E(max) values for carbachol or sodium nitroprusside in the presence of PAF. CONCLUSIONS: Our results suggest that PAF does not modify the endothelium-dependent, endothelium-independent or electrical field stimulation-induced NANC relaxation responses in isolated rabbit corpus cavernosum strips.     

Relaxation mechanisms of neferine on the rabbit corpus cavernosum tissue in vitro

Aim： To investigate the relaxation mechanisms of neferine （Nef） on the rabbit corpus cavemosum tissue in vitro. Methods： Strips of rabbit corpus cavemosum were mounted in organ chambers. The effects of Nef were examined on isolated muscle strips precontracted with phenylephrine （PE） alone, in the presence of NW-nitro-L-arginine （LNNA, a nitric oxide synthase inhibitor）, 1-H-[ 1,2,4]oxadiazolo[4,3-tx]quinoxalin- 1-one （ODQ, a guanylyl cyclase inhibitor）, indomethacin （cyclooxygenase inhibitor）, tetraethylammonium （Ca^2＋ -activated K^＋ channel blocker）, 4-aminopiridine （4-AP ,voltage dependent K^＋ channel blocker） and glibenclamide （ATP sensitive K^＋channel blocker）. The effects of Nef on KCl-induced contraction of isolated muscle strips were also investigated. The procedure of calcium absencecalcium addition was designed to observe the effect of Nef on two components of the contractile responses to PE based on the source of Ca^2＋ （extracellular vs. intracellular）. Results： Corpus cavemosum strips relaxed in response to Nef （10-9-10-4 mol/L） in a concentration-dependent manner with an IC50 of 4.60 × 10^-6 mol/L. However, they were not affected by LNNA, ODQ, indomethacin or K^＋-channel blockers. Nef （10^-6 mol/L, 10^-5 mol/L） concentration dependently reduced the maximal contraction response of isolated strips induced by KC1 to 79.3% ± 5.5% and 61.5% ±3.2%, respectively （P 〈 0.01）. In the calcium absence-calcium addition procedure, Nef 10.5 mol/L inhibited both intracellular calcium-dependent and extracellular calcium-dependent contraction induced by PE （2 × 10^5 mol/L） （P 〈 0.05）. The inhibition ratios were 26.2% ± 5.4% and 48.3% ±7.6%, respectively. Conclusion： The results of the present study suggest that Nef possesses a relaxant effect on rabbit corpus cavemosum tissues, which is attributable to the inhibition of extracellular Ca^2＋ influx and the inhibition of release of intracellular stored Ca^2＋, but not mediated by the     

The neuronal and endothelium-dependent relaxing responses of human corpus cavernosum under physiological oxygen tension last longer than previously expected

BACKGROUND: Intracavernosal oxygen tension varies greatly in the process of erection. Blood extracted from the human penis demonstrates an increase from approximately 30 mmHg Po(2) 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% CO(2) in N(2) and O(2). 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.     

Effects of epoxygenases on the nonadrenergic noncholinergic relaxant responses induced by electrical field stimulation in rabbit corpus cavernosum

We aimed to investigate the effects of epoxygenases on electrical field stimulation (EFS)‐mediated nitric oxide (NO)‐dependent and NO‐independent nonadrenergic noncholinergic (NANC) relaxations in isolated rabbit corpus cavernosum. The tissues of 20 male adult albino rabbits (2.5–3 kg) were suspended in organ baths containing aerated Krebs solution, and isometric contractions were recorded. EFS‐mediated NANC relaxations were obtained on phenylephrin (3 × 10^?5 M)‐contracted tissues in the presence of guanethidine (10^?6 M) and atropine (10^?6 M). Miconazole (10^?9–10^?4 M), 17‐octadecynoic acid (ODYA) (10^?10–10^?5 M), 14,15‐epoxyeicosatrienoic acid (EET) (10^?11–10^?8 M), 11,12‐EET (10^?12–3 × 10^?8 M) and 20‐hydroxyeicosatetraenoic acid (HETE) (10^?11–3 × 10^?8 M) were added cumulatively (n = 5–7 for each set of experiments). For NO‐independent relaxations, N^ω‐nitro‐l ‐arginine methyl ester (l ‐NAME) (10^?4 M) was added before a group of experiments. Depending on the concentration, miconazole, 17‐ODYA, 14,15‐EET, 11,12‐EET, and 20‐HETE significantly enhanced both NO‐dependent and NO‐independent EFS‐mediated relaxations (p < 0.05). Epoxygenases showed similar effect on NO‐dependent and NO‐independent relaxant responses except 20‐HETE which caused significantly more enhanced relaxation on NO‐dependent responses (p < 0.05). No drug caused a significant relaxation response on tissues contracted with phenylephrine. Epoxygenases contribute to EFS‐mediated NO‐dependent and NO‐independent NANC relaxations by presynaptic mechanisms, offering a new treatment alternative for erectile dysfunction which needs to be explored in further in vivo, molecular and clinical studies.     

Expression of vascular endothelial growth factor and angiopoietins in human corpus cavernosum

OBJECTIVE

To evaluate the expression of the angiogenic factors vascular endothelial growth factor (VEGF) and angiopoietins (Ang) 1 and 2, in normal human penile erectile tissue.

MATERIALS AND METHODS

Penile fragments were removed from four young healthy organ donors (aged 17–28 years), and processed for immunohistochemical studies for VEGF, Ang1 and Ang2, and their specific receptors (VEGFR1 and 2, and Tie2, respectively). Molecular analysis was used to confirm the expression of VEGF and Angs in erectile tissue.

RESULTS

VEGF and VEGFR1 expression was restricted to smooth muscle cells (SMCs). VEGFR2 was detected mainly in the endothelium lining and to a lesser extent in the SMC. Ang1 had a scattered distribution mostly in the perivascular SM layer, showing co‐localization with VEGF. Tie2 was faintly detected in the endothelial cells. Ang2 was not detected by immunohistochemical studies, but the use of the same antibody in molecular analysis confirmed Ang2 expression in human corpus cavernosum.

CONCLUSIONS

We show for the first time the co‐localization of VEGF and Ang1 in the SMC, suggesting an interaction for vessel stabilization. Ang2 seems to be available for neoangiogenesis, if challenged. Studies of endothelial markers, growth factors and specific receptors are useful for understanding vascular organization and angiogenesis in normal human erectile tissue. This knowledge will be fundamental for developing newer therapeutic approaches to prevent or even cure erectile dysfunction.     

Effects of NCX 4050, a new NO donor,in rabbit and human corpus cavernosum

The effects of NCX 4050, a drug belonging to a new class of NO donors, was investigated in isolated preparations of human and rabbit corpus cavernosum (CC) and in human foetal corpora cavernosa (hfCC) smooth muscle cells. In strips of rabbit CC, NCX 4050 (0.001-100 microM) induced a concentration-dependent relaxation which was influenced neither by Nw-nitro-l-arginine-methyl-ester (l-NAME; 100 microm) nor by endothelium deprivation. The NCX 4050-induced relaxation was significantly reduced by the guanylate cyclase inhibitor 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 1 microm) and enhanced by a specific phosphodiesterase 5 inhibitor, sildenafil (300 nm). Moreover, NCX 4050 (0.01-1 microm), induced a concentration-dependent potentiation of the relaxant response induced by electrical field stimulation (EFS) in rabbit preparations pre-treated with guanethidine and indomethacin. The relaxant effect of NCX 4050 was similar to that obtained by increasing concentrations (0.001-100 microm) of sodium nitroprusside (SNP) in either rabbit or human preparations. To further investigate the activity of NCX 4050 on human corpora cavernosa, we exposed cultured hfCC smooth muscle cells to increasing concentrations of NCX 4050 and SNP. We found that both compounds dose-dependently reduced cell proliferation. The antiproliferative effect of all the concentration tested of NCX 4050 was completely blocked by ODQ (1 microm). These results suggest that in rabbit and human corpora cavernosa NCX 4050 acts by activating guanylate cyclase activity, induces smooth muscle relaxation and quiescence. Our results provide a rationale for a possible future use of NCX 4050 in the pharmacotherapy of erectile dysfunction linked to an impaired release of NO from the endothelium.     

Relaxant effect and possible mechanism of 17-nor-subincanadine E in rabbit corpora cavernosa

Compounds with dual action on cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) may be a treatment option for erectile dysfunction, as they not only promote penile erection but also prevent the upregulation of phosphodiesterase-5. In this study, we examined the possible relaxant effect and mechanism of 17-nor-subincanadine E (SEC, 0.2–200 µmol l⁻¹), a plant-derived alkaloid, in rabbit corpus cavernosum (RbCC) strips that had been precontracted by exposure to phenylephrine (10 µmol l⁻¹) or a high concentration of K⁺ (60 mmol l⁻¹) in vitro. In addition to SEC''s effect on cAMP and cGMP levels, electrical field stimulation (EFS) in phenylephrine-precontracted RbCC and calcium chloride (1–100 mmol l⁻¹) evoked responses in depolarized RbCC were analysed. SEC relaxed the phenylephrine-precontracted RbCCs in a concentration-dependent manner. Atropine, guanethidine and N-ω-nitro-ℓ-arginine methyl ester (L-NAME) did not have any effect on the relaxation of RBCCs. When 1H-^{1, 2, 4}oxadiazole[4,3-a] quinoxalin-1-one (ODQ) was added, it effectively blocked the relaxant response of SEC. Although SEC enhanced the maximal relaxation produced by sodium nitroprusside (SNP) and forskolin in phenylephrine-precontracted cavernosal smooth muscle, it caused a decrease in the maximal contractile response induced by calcium chloride in depolarized RbCCs. The relaxant effect of SEC was paralleled by an increase in the tissue levels of the cyclic nucleotides cAMP and cGMP. We conclude that SEC promotes the relaxation of RbCC, possibly favouring cAMP and cGMP accumulation and calcium blockade. This novel mechanism could be useful for patients who do not benefit from phosphodiesterase inhibitors and for those with endothelial and nitrergic dysfunction, such as patients with diabetes, hypertension and dyslipidaemias.     

Nitric oxide mediates relaxation in rabbit and human corpus cavernosum smooth muscle

Summary We investigated in vitro the relaxant effect of exogenous acetylcholine (ACh) and electric-field stimulation (EFS) on rabbit and human corpus cavernosum smooth muscle strips (CC) precontracted with phenylephrine. The effects of EFS and ACh were monitored alone, after muscarinic receptor blockade and after inhibition of nitric oxide (NO) formation with l-N-nitroarginine (l-NOARG). In rabbit und human CC, both atropine and l-NOARG abolished the relaxant effects of ACh. The relaxant effects of EFS, however, were only slightly reduced by atropine to 97.5±17.5% in human CC and to 89.0±6.1% in rabbit CC. l-NOARG further reduced the EFS effects to 0.8±1.7% in human CC and to 16.2±8.7% in rabbit CC. In strips obtained from impotent patients with diabetes mellitus, the relaxant effects appeared to be significantly less than in strips from nondiabetic impotent men. Tetrodotoxin blocked the relaxant EFS effects in human and rabbit strips completely. The data indicate the important role of NO in cholinergically induced relaxation of cavernous smooth muscle in rabbits and humans. Our findings support the idea of NO as the nonadrenergic noncholinergic neurotransmitter in penile erection in both species. Rabbit erectile tissue might serve as an in vitro animal model for further investigation.     

低氧对SD大鼠阴茎海绵体平滑肌纤维化的影响

目的:探讨低氧对SD大鼠阴茎海绵体平滑肌纤维化的影响。方法:体外培养阴茎海绵体平滑肌细胞,免疫组化鉴定细胞;常规氧浓度(21%O2浓度)分别培养12、24、48、72h作为对照,低氧(1%O2浓度)干预12、24、48、72h,RT-PCR分别测定各组TGF-β1、Ⅰ型胶原、Ⅲ型胶原的相对表达量。结果:体外培养的阴茎海绵体平滑肌细胞生长良好,抗平滑肌α-肌动蛋白单克隆抗体免疫组化染色阳性;RT-PCR结果提示TGF-β1、Ⅰ型胶原、Ⅲ型胶原的相对表达量在48h内与低氧时间成正相关,时间进一步延长不能增加其相对表达量。结论:在低氧环境下,SD大鼠阴茎海绵体平滑肌细胞的TGF-β1、Ⅰ型胶原、Ⅲ型胶原的相对表达量随时间的延长逐渐增加,48h达到最大值。低氧可导致SD大鼠阴茎海绵体平滑肌纤维化。     

Effect of sodium nitropmsside on hemodynamics of corpus cavemosum in Chinese

Aim: To study the effect of sodium nitroprusside (SNP) on the hemodynamics of corpus cavemosum in Chinese men with erectile dysfunction (ED). Methods: In 68 ED patients receiving intracavemous injection (ICI) of SNP, the cavemous hemodynamics were studied by Doppler ultrasonography. Results: The peak flow velocity (PFV), the artery diameter (Ad), the mean velocity of arterial blood (MV) and the vein diameter (Vd) were significantly higher after ICI of SNP than before ICI, but the end diastolic velocity (EDV) did not change significantly. Conclusion: The increase in Vd after SNP suggests that the venous outflow is not invariably decreased during penile election.     

2型糖尿病大鼠血浆同型半胱氨酸与阴茎海绵体内NOS和内源性CO的相关性研究

目的:研究2型糖尿病性大鼠血浆同型半胱氨酸(Hcy)与阴茎海绵体内NOS和内源性CO的相关性。方法:选取3月龄雄性Wistar大鼠50只,随机选取10只为对照组(A组);高糖高脂饲料饲养4周后从其他40只大鼠中筛选出30只构建成功的糖尿病(DM)大鼠模型,随机分成3组:DM大鼠组(B组);胰岛素治疗组(C组)和叶酸+维生素B12治疗组(D组)。8周及12周后注射阿朴吗啡观察各组大鼠阴茎勃起情况。12周后测各组大鼠血浆总Hcy含量及阴茎海绵体内NOS活性和CO含量。结果:与A组比较,B组大鼠血浆Hcy浓度明显升高,阴茎勃起功能明显降低,阴茎海绵体NOS活性和CO含量均下降,差异有显著性(P<0.01)。2型DM大鼠中高Hcy血症发生率为55%。与B组比较,C组和D组中大鼠血浆Hcy浓度显著下降,阴茎勃起功能、阴茎海绵体NOS活性均升高(P<0.01),Hcy与NOS(rA=-0.89,rB=-0.76,rC=-0.91,rD=-0.91)及CO含量(rA=-0.82,rB=-0.77,rC=-0.93,rD=-0.81)均呈负相关。结论:2型DM大鼠血浆中的高Hcy可能是引起阴茎海绵体NOS活性下降、CO含量下降,进而导致DM ED发病的分子机制之一。胰岛素、叶酸和维生素B12可以改善DM大鼠的勃起功能,提高阴茎海绵体NOS活性和CO含量。     

Effect of magnesium on the function of the rabbit corpus cavernosum

Contraction and relaxation of the smooth muscle, including the corpus cavernosum, are mediated by changes in the intracellular concentration of calcium. Since magnesium modulates the movement of calcium it can modify the function of the erectile tissue. We designed this study to investigate the effects of magnesium in doses ranging from 5 to 30 mM on the function of the rabbit corpus cavernosum in vitro. The resting tension of tissue strips was significantly reduced by exposure to a solution high in magnesium (5–30 mM). The contractile response to field stimulation under resting conditions, and the contraction to phenylephrine, were significantly decreased by magnesium (5–30 mM). There were no differences in the contractile strength of the corpus cavernosum to KCl. Although the relaxation induced by field stimulation under preincubation with 200 M phenylephrine was abolished in the presence of 30 mM magnesium, there were no differences at a concentration of 5 mM or of 10 mM magnesium. The relaxation induced by sodium nitroprusside under precontraction with 200 M phenylephrine was further increased by magnesium dose dependently. A high concentration of magnesium (30 mM) enhanced both bethanechol-induced and ATP-induced relaxations under precontraction with phenylephrine. Our study demonstrated that magnesium reduced the receptor-mediated contraction of the rabbit corpus cavernosum and enhanced the relaxation of this tissue induced by sodium nitroprusside, bethanechol, and ATP.     

Effect of aldosterone on isolated human penile corpus cavernosum tissue

OBJECTIVE

To clarify the physiological effects of aldosterone on human penile corpus cavernosum (hPCC) tissue, as aldosterone has a wider physiological action than just the maintenance of electrolyte balance, and there are mineralocorticoid receptors, i.e. aldosterone receptors, in hPCC tissue.

MATERIALS AND METHODS

Specimens of hPCC were obtained from 10 patients (mean age 38 years, range 21–75), with informed consent and approval by the local ethics committee. One patient had a penectomy because of penile cancer, and nine had a penile biopsy because of erectile dysfunction. Patients with diabetes mellitus, hypertension or ischaemic heart disease were excluded. In a pharmacological study we evaluated the effect of aldosterone on the isolated hPCC tissues.

RESULTS

Aldosterone caused no significant change in resting tension and did not affect the nitric oxide‐dependent relaxation reaction. However, the dose–response curve of noradrenaline was shifted to the left when the strip preparation was treated with aldosterone (1 × 10^?5m ) for 20 min before administering noradrenaline. Moreover, the shift to the left was completely blocked when spironolactone (anti‐aldosterone agent) was added as a pre‐treatment. Pre‐treatment with aldosterone also significantly extended the mean (sem ) time required to reach 50% relaxation of a noradrenaline‐induced contraction, of 9.3 (1.5) min, vs the control, of 5.2 (1.0) min (P = 0.002).

CONCLUSION

Aldosterone has no direct contractile action or a relaxant action on human penile cavernous tissue, but acts to significantly enhance the noradrenaline‐induced contraction. The effect on the noradrenaline‐induced contraction is probably caused by aldosterone enhancing the affinity of the α‐receptors for noradrenaline in hPCC. We suggest that aldosterone acts to enhance contraction of hPCC tissue, and is one of the restraining factors for human penile erection.     

Three-dimensional mapping and comparative analysis of the distal human corpus cavernosum and the inflatable penile prosthesis

The intricate anatomy of the corpus cavernosum in both the flaccid and tumescent state has not been fully elucidated. We report our experience using a three-dimensional (3D) scanner to reconstruct cadaveric casts and compare them with 3D images of two prototypes of penile prosthesis. Two different models of the Titan Coloplast inflatable penile prosthesis were analyzed using a 3D scanner. The first was the standard model and the second was a newer model with a rounder silicone tip. Two cadaveric phalluses were harvested using Smooth-Cast 300Q polyurethane molding. The molds were excised and scanned along side the penile prosthesis. 3D scans were completed and analyzed using Leios Mesh software, and GOM Inspect software. The 3D scans demonstrated the mean human corporal radii 2 mm from the distal tip to be 36.51 mm (36.01–37.0 mm), which is an obtuse angle. The standard Titan penile prosthesis spherical radius at the same level was 202.52 mm, while the new silicone tip prosthesis had a radius of 139.33 mm. 3D mapping further demonstrated the trajectory of the cavernosa appeared curvilinear and the distal ends appeared blunt. The use of cadaveric cavernosal molds in combination with the 3D scanner allowed us to accurately image the corpus cavernosum for the first time. Our findings suggest that anatomically accurate corporal tips appear to be relatively blunt and that the new Titan silicone tip penile prosthesis more closely resembles the human corporal tip.