Prevention and reversal of diabetic nephropathy in db/db mice treated with alagebrium (ALT-711)

BACKGROUND: Alagebrium (ALT-711) has been shown to improve renal dysfunction in animal models of diabetes. METHODS: To test its effects in diabetic nephropathy (DN), ALT-711 was administered (1 mg/kg daily i.p.) to 9-week-old female db/db mice (n = 15, group A1) for 3 weeks and to 3-month-old (n = 15, group A2), 7-month-old (n = 7, group A3), and 12-month-old (n = 5, group A4) female db/db mice for 12 weeks, while a similar number of diabetic and nondiabetic mice were used as controls. The epsilonN-carboxymethyllysine (CML) levels in serum, urine, skin, and kidney tissue were measured by enzyme-linked immunosorbent assay. The renal morphometric parameters were assessed by electron and light microscopy. RESULTS: By the 3rd week of treatment, the serum CML level decreased by 41%, and the urinary CML concentration increased by 138% from baseline, while the urinary albumin/creatinine ratio was lower (p < 0.05) in diabetic and nondiabetic group A1 mice. After 3 months of treatment, serum, skin, and kidney CML levels and urinary albumin/creatinine ratio were lower (p < 0.05) and the urinary CML levels higher (p < 0.05) in treated group A2, A3, and A4 animals compared with groups which received phosphate-buffered saline, with a similar pattern observed in nondiabetic mice. The renal morphological parameters characteristic of DN decreased in treated compared with untreated mice. CONCLUSION: Alagebrium may prevent, delay, and/or reverse established DN in db/db mice by reducing the systemic advanced glycation end product pools and facilitating the urinary excretion of advanced glycation end products.     

多聚ADP-核糖聚合酶抑制剂联合西地那非改善糖尿病大鼠勃起功能的研究

目的 探讨多聚ADP-核糖聚合酶抑制剂(PJ-34)联合西地那非对糖尿病大鼠勃起功能的影响.方法 40只雄性SD大鼠随机分为正常对照组、糖尿病+西地那非组、糖尿病+PJ-34组、糖尿病+PJ-34+西地那非组.测定各组大鼠阿扑吗啡诱导下的性行为变化;电刺激盆神经测定各组大鼠阴茎海绵体内压(ICP)及平均周围动脉压(MAP),然后取海绵体组织测定Caspase-3活性.结果 Caspase-3活性在糖尿病大鼠中显著升高,PJ-34治疗可有效抑制其活性.糖尿病+西地那非组、糖尿病+PJ-34组性行为能力及ICP/MA均低于正常对照组,PJ-34与西地那非联合应用疗效显著高于单一用药.结论 PJ-34联合西地那非可以显著改善糖尿病大鼠的勃起功能,为糖尿病性勃起功能障碍治疗方法 的探索提供了新的思路.     

Effect of combination endothelial nitric oxide synthase gene therapy and sildenafil on erectile function in diabetic rats

Erectile dysfunction associated with diabetes mellitus is caused in part by disordered endothelial smooth muscle relaxation, neuropathy, and a decrease in cavernosal nitric oxide synthase (NOS) activity. The purpose of this study was to determine whether a combination of sildenafil and adenoviral gene transfer of endothelial NOS (eNOS) could enhance the erectile response in diabetic rats. Five groups of animals were utilized: (1) age-matched control rats, (2) streptozotocin (STZ)-induced diabetic rats (60 mg/kg i.p.), (3) STZ-rats + sildenafil (2 mg/kg i.v.), (4) STZ-rats transfected with AdCMVbetagal or AdCMVeNOS, and (5) STZ-rats transfected with AdCMVeNOS +sildenafil (2 mg/kg i.v.). At 2 months after i.p. injection of STZ, groups 4 and 5 were transfected with the adenoviruses and 1-2 days after transfection, all animals underwent cavernosal nerve stimulation (CNS) to assess erectile function. Cyclic 3',5'-guanosine monophosphate (cGMP) levels were assessed in the cavernosal tissue. STZ-diabetic rats had a significant decrease in erectile function as determined by the peak intracavernosal pressure (ICP) and total ICP (area under the erectile curve; AUC) after CNS when compared to control rats. STZ-diabetic rats+AdCMVeNOS had a peak ICP and AUC, which were similar to control animals. STZ-diabetic rats administered sildenafil demonstrated a significant increase in peak ICP at the 5 and 7.5 V settings, while the AUC was significantly increased at all voltage (V) settings. The increase in both ICP and AUC of STZ-diabetic rats transfected with AdCMVeNOS at all V settings was greater than STZ-diabetic rats transfected with AdCMVbetagal. STZ-diabetic rats transfected with AdCMVeNOS and administered sildenafil had a significant increase in total ICP that was greater than eNOS gene therapy alone. Cavernosal cGMP levels were significantly decreased in STZ-diabetic rats, but were increased after transfection with AdCMVeNOS to values greater than control animals. In conclusion, overexpression of eNOS and cGMP in combination with sildenafil significantly increased both the peak ICP and total ICP to CNS in the STZ-diabetic rat, which was similar to the response observed in control rats. Moreover, the total erectile response was greater in STZ-diabetic rats receiving eNOS gene therapy plus sildenafil than STZ-rats receiving sildenafil or eNOS gene therapy alone.     

西地那非治疗原发性勃起功能障碍的效果分析

目的 评估西地那非治疗原发性勃起功能障碍(ED)的疗效和安全性. 方法 104例符合原发性ED的患者分为2组:对照组46例,接受性知识和性技巧指导;治疗组58例,同房前1 h口服西地那非50 mg,根据前期4次以上的疗效和耐受性,进行药物剂量调整.比较治疗前后国际勃起功能指数调查表5个简化问题(IIEF-5)评分,评估治疗后临床总有效率、无ED比例及不良反应发生率.2组均治疗3个月,停药后1个月和3个月时再次评估疗效. 结果 治疗3个月末,对照组、治疗组治疗前后IIEF-5中位评分分别为5.2分和12.6分、4.2分和19.8分;无ED者分别为12例(26.1％)、56例(96.6％),临床总有效率分别为27.7％、97.2％;停药1个月无ED者分别为8例(17.4％)、56例(96.6％),临床总有效率分别为19.4％、97.1％;停药3个月无ED者分别为7例(15.2％)、55例(94.8％),临床总有效率分别为16.4％、96.4％.治疗组发生药物不良反应16例(27.6％),对照组5例(10.9％),组间差异有统计学意义(P＞0.05);多数不良反应短暂、轻微,随治疗时间延长逐渐减弱到消失,无因药物不良反应而中断服药者. 结论 西地那非治疗原发性勃起功能障碍安全有效,疗效维持良好.     

Yohimbine enhances the effect of sildenafil on erectile process in rats

Combining the centrally acting drug yohimbine with the peripheral conditioner sildenafil might be an approach to erectile dysfunction cases in which sildenafil alone failed. This work aimed to investigate the effect of yohimbine on sildenafil-induced facilitation of erectile process. Erectile responses to electrical stimulation of the cavernous nerve in anesthetized male rats were recorded. Intracavernosal pressure/systemic arterial pressure (ICP/SAP) was calculated, 1 and 5 min after intravenous administration of sildenafil, yohimbine or a combination of both. Changes in sexual arousal and copulatory performance indices were compared before and after these injections using behavioral mating experiments. It was shown that systemic administration of sildenafil produced a significant increase in ICP/SAP than control at doses >or=10 micromol kg(-1). Yohimbine alone failed to potentiate erectile responses but yohimbine (1 micromol kg(-1)) significantly potentiated the effect of sildenafil 1-10 micromol kg(-1) and 1 mmol kg(-1), 1 and 5 min after injection. Potentiation of ICP/SAP induced by their combination was greater than the sum of the effects of the corresponding doses of either drug at the same time interval. A nonsignificant additional decrease in SAP than sildenafil-induced was observed if administered with yohimbine. Addition of sildenafil to yohimbine significantly enhanced the effect of the latter on intromission frequency, intercopulatory interval and the number of ejaculations per session. It is concluded that yohimbine may enhance and prolong the effect of sildenafil on erectile process without additional hypotension. Sildenafil may enhance the central effects of yohimbine on erection; it amplifies the effect of yohimbine on male copulatory performance but not on sexual motivation. The potential beneficial effect of the combination was found to be more pronounced on the central component than on the peripheral component of the erectile process.     

PDE_5基因特异性siRNA改善糖尿病性勃起功能障碍大鼠勃起功能的研究

目的 探讨人鼠PDEs基因siRNA对糖尿病性勃起功能障碍(DM ED)大鼠PDE,基因表达的抑制作用及其对DMED大鼠勃起功能的影响.方法 构建可同时表达2条针对大鼠PDEs基因的shRNA重组腺病毒;50只雄性SD大鼠随机取10只作为正常对照.其余建立DM ED人鼠模型,随机分为实验组、阴性对照组和空白对照组,分别将重组腺病毒rAd-rPDEs-shRNA、腺病毒rAd-mock及生理盐水注射于阴茎海绵体.注射后第7天,电刺激盆神经测定各组大鼠阴茎海绵体内压(ICP)及平均周围动脉压(MAP),然后取海绵体组织通过RT-PCR和Western blot分别检测PDE5基因mRNA及蛋白的表达.结果 ICP/MAP实验组和正常对照组显著高于阴性对照组和窄白对照组(P＜0.05),实验组和正常对照组间无显著性差异(P＞0.05);RT-PCR和Western blot 分析,实验组大鼠PDE5基因mRNA和蛋白表达均显著低于阴性对照组和空白对照组(P＜0.05).结论 PDE5基因shRNA重组腺病毒转染可以改善DMED大鼠的勃起功能,为DMED治疗方法的探索提供了新的思路.     

The effect of PDE5 inhibition on the erectile function in streptozotocin-induced diabetic rats

The aim of this study was to assess the effect of phosphodiesterase 5 inhibitor, DA-8159, on erectile function throughout the quantitative analysis of vascular endothelial cell, smooth muscle (SM), TGF-beta1 expression in rat corpus cavernosum and measurement of intracavernous pressure (ICP) in diabetic rats. DA-8159 (0, 5, 10, 20 mg/kg) was administered orally once a day to diabetic rats. After 8 weeks, immunohistochemistry and computerized image analysis were performed to quantify the percent area within the Corpora Cavernosa occupied by the endothelial cells, SM cells and fibrotic tissues. ICP/mean arterial pressure (MAP) was also measured by electrostimulation of the cavernous nerve. Diabetic rats showed a significant decrease in the SM and endothelial cell content, and an increase in the TGF-beta1 expression level within the cavernosa areas compared to the normal rats. The mean cavernous SM, endothelial cell content and TGF-beta1 expression level were 9.7+/-0.7, 4.5+/-0.7 and 17.9+/-2.1%, respectively. DA-8159 prevented reduction of SM (12.3+/-0.4% (5 mg/kg), 13.8+/-0.4% (20 mg/kg)) and endothelial cell content (5.6+/-0.5% (5 mg/kg), 6.3+/-0.6% (20 mg/kg)). Immunoreactivity of TGF-beta1 and intracorporal fibrosis were also significantly lower in DA-8159-treated groups (11.8+/-1.2% (5 mg/kg), 9.5+/-1.1% (20 mg/kg)). Electrostimulation of the cavernous nerve induced significant increase in maximum ICP (62.2+/-13.6 mmHg in 10 mg/kg vs 37.5+/-17.5 mmHg in diabetic group) and area under the curve of the ratio of ICP/MAP (8891.09+/-1957 in 10 mg/kg vs 6315.87+/-2272 in diabetic group). These results suggest that subchronic treatment of DA-8159 can prevent the development of erectile dysfunction (ED), and provides a rationale for the use of DA-8159 as treatment of diabetic ED.     

左卡尼汀联合西地那非对雄性糖尿病大鼠生殖内分泌功能的保护作用

目的:初步探讨左卡尼汀与西地那非片在保护糖尿病(DM)大鼠生殖内分泌功能中的作用。方法:40只体重为200～230 g的雄性SD大鼠随机均分为5组:A组为正常对照组,B组为DM大鼠模型组,C组为DM大鼠给予西地那非[5 mg/(kg.d)]治疗组,D组为DM大鼠给予左卡尼汀[300 mg/(kg.d)]治疗组,E组为DM大鼠给予左卡尼汀[300 mg/(kg.d)]联合西地那非[5 mg/(kg.d)]治疗组。各组大鼠治疗6周后分别进行血睾酮(T)、卵泡刺激素(FSH)、黄体生成素(LH)的检测。结果:糖尿病大鼠治疗6周后,血清T,FSH、LH含量,A组:T为(25.25±2.67)nmol/L,FSH为(5.78±0.61)IU/L,LH为(625.21±43.45)ng/L;B组:T为(9.63±1.71)nmol/L,FSH为(1.98±0.42)IU/L,LH为(479.89±27.62)ng/L:C组:T为(18.98±3.07)nmol/L,FSH为(5.08±0.33)IU/L,LH为(586.57±31.72)ng/L;D组:T为(16.18±2.65)nmol/L,FSH为(4.63±0.30)IU/L;LH为(540.78±25.52)ng/L;E组:T为(23.65±2.66)nmol/L,FSH为(5.59±0.48)IU/L,LH为(621.53±36.40)ng/L。各组血清T,FSH、LH含量之间比较,B组均显著低于A、C、D、E组(P均<0.01);C、D组均显著低于A、E组(P均<0.05),而C、D组之间比较,差异均无显著性(P>0.05);E组与A组比较,差异也均无显著性(P>0.05)。结论:西地那非片与左卡尼汀灌胃6周后均可增加DM大鼠血清T、FSH、LH的水平,而两者联合用药时,T、FSH、LH增加水平比单独用药更明显,显示联合用药在保护雄性DM大鼠生殖内分泌功能方面效果更佳。     

还原型谷胱甘肽在预防糖尿病大鼠勃起功能障碍中的研究

目的探讨还原型谷胱甘肽(GSH)在预防糖尿病大鼠勃起功能障碍中的作用。方法通过腹腔注射链脲佐菌素65mg/kg建立糖尿病大鼠模型,然后随机分成DM组和DM+GSH组,DM+GSH组每天肌肉注射GSH200mg/kg。10周后观察大鼠勃起功能,并获取海绵体组织检测其谷胱甘肽、一氧化氮合酶(NOS)与丙二醛(MDA)水平,用TUNEL法检测细胞凋亡。结果成功建立糖尿病大鼠模型。与未注射GSH的DM组相比,DM+GSH组和正常对照组(C组)勃起功能更好,勃起率分别是20%,62.5%和100%。GSH水平DM+GSH组和C组明显比DM组高,其3组含量每克蛋白分别是(75.83±15.62)、(61.47±8.65)和(35.03±12.29)mg(P<0.05);NOS水平在DM+GSH组每毫克蛋白为(133.9±31.9)U,与正常对照组每毫克蛋白为(142.2±31.2)U相当,但较DM组每毫克蛋白为(58.4±18.9)U高(P<0.05);MDA含量在DM组每毫克蛋白为(3.71±0.62)nmol,明显高于正常对照组和DM+GSH组(P<0.05),这两组每毫克蛋白为(2.08±0.34)nmol和(2.44±0.28)nmol;细胞凋亡率在DM组、DM+GSH组和C组的分别是(22.6±3.6)%、(10.8±1.7)%和(7.2±2.1)%(P<0.05)。结论还原型谷胱甘肽对糖尿病大鼠阴茎组织有较好的抗氧化作用,能减少细胞凋亡,对延缓糖尿病性ED的发生有一定的作用。     

Chronic sildenafil improves erectile function and endothelium-dependent cavernosal relaxations in rats: lack of tachyphylaxis

OBJECTIVES: Sildenafil is a widely-prescribed effective on-demand treatment of erectile dysfunction (ED). Chronic treatment with sildenafil could help patients with ED. METHODS: The effects of an 8-week long treatment with sildenafil (60 mg/kg/d sc) in male Sprague Dawley rats were evaluated on electrically-elicited erectile responses in vivo before and after an acute injection of sildenafil (0.3mg/kg iv). In addition, endothelium-dependent and -independent relaxations of strips of corpus cavernosum in vitro were examined. All experiments were performed 36 hours after the last injection of sildenafil. RESULTS: Endothelium-dependent relaxations of cavernosal strips to acetylcholine were enhanced after chronic treatment with sildenafil while relaxations to A23187 or sodium nitroprusside were unchanged. Frequency-dependent erectile responses elicited by cavernous nerve stimulation were significantly improved. Moreover, the erectile responses to acute sildenafil were greater in chronically-treated rats with sildenafil. CONCLUSIONS: This is the first report providing experimental support for chronic dosing with sildenafil which could be of use for patients that are poor responders to on-demand treatment. Chronic sildenafil may regulate the transduction pathway leading to the activation of eNOS but has no effect on NO bioavailability or on the cGMP pathway, thereby eliminating a possible concern for tachyphylaxis.     

Indications and early results of sildenafil (Viagra) in erectile dysfunction

Objectives. To assess the acceptability, feasibility, and early results of sildenafil (Viagra) in a nonselected cohort of 316 patients (median age 58 years) who sought treatment for male sexual dysfunction during a 10-week period.Methods. Erectile status and activity were evaluated by questionnaire; erectile function was assessed by pharmacologic testing and visual sexual stimulation. Cardiovascular contraindications were assessed. Patients selected for the trial received treatment for 2 months. Results based on the possibility of penetration and individual satisfaction (scale from 0 to 10) were classified as good, fair, or bad. Multifactorial analysis was performed to define factors influencing the response to sildenafil.Results. Twenty-five percent of the patients from the initial cohort refused or did not meet the criteria for oral treatment; 25% of the remaining had a cardiovascular contraindication. At the end of the trial, 157 patients (88.7%) had completed the study; the efficacy of and satisfaction with sildenafil were considered good for 50 (31.84%), fair for 46 (29.29%), and bad for 61 (38.85%). Spontaneous nocturnal erections, organic etiologies, especially cavernovenous impotence, and previous treatment with self-intracavernous injections were significant factors influencing responses to oral treatment. Finally, 32% of the patients after completing the trial (17.2% of the initial cohort) were using sildenafil as their sole treatment, 34% chose self-intracavernous injections, and 25% decided to alternate between oral and local therapy.Conclusions. In the present study, sildenafil had a 60% efficacy rate and was chosen as the sole treatment by only 30% of the patients tested. We propose pretreatment tests to help to predict the response to this medication.     

Effect of hydrogen sulphide‐donating sildenafil (ACS6) on erectile function and oxidative stress in rabbit isolated corpus cavernosum and in hypertensive rats

OBJECTIVE

To study the effect of the H₂S‐donating derivative of sildenafil (ACS6) compared to sildenafil citrate and sodium hydrosulphide (NaHS) on relaxation, superoxide formation and NADPH oxidase and type 5 phosphodiesterase (PDE5) expression in isolated rabbit cavernosal tissue and smooth muscle cells (CSMCs), and in vivo on indices of oxidative stress induced with buthionine sulphoximine (BSO).

MATERIALS AND METHODS

Relaxation was studied in an organ bath in response to carbachol and after incubation with interleukin‐1β for 12 h. CSMCs were incubated with tumour‐necrosis factor‐α or the thromboxane A₂ (TXA₂) analogue, U46619, with or with no sildenafil citrate, ACS6 or NaHS for 16 h. Superoxide formation and the expression of p47^phox (an active subunit of the NADPH oxidase complex) and PDE5 protein was then assessed using Western blotting. Rats were also treated with BSO (with or with no sildenafil citrate or ACS6) for 7 days; cavernosal cGMP, cAMP, glutathionine and plasma TXA₂ and 8‐isoprostane F_2α was measured by enzyme‐linked immunosorbent assay.

RESULTS

ACS6 and sildenafil citrate relaxed cavernosal smooth muscle equipotently; NaHS alone had little effect at up to 100 µm . The formation of superoxide and expression of p47^phox and PDE5 was reduced by ACS6, sildenafil citrate and NaHS (order of potency: ACS6 > sildenafil citrate > NaHS). The effects of ACS6 were blocked by inhibitors of protein kinase A (PKA) and PKG. In rats treated with BSO, both ASC6 and sildenafil citrate reduced the increased plasma levels of TXA₂ and 8‐isoprostane F_2α but increased cGMP, cAMP and glutathionine levels in corpus cavernosum.

CONCLUSIONS

By virtue of a dual action on PKA and PKG activation, ACS6 not only promotes erection, acutely, but might also have a long‐term beneficial effect through inhibition of oxidative stress and downregulation of PDE5.     

The protective effect of aminoguanidine on erectile function in diabetic rats is not related to the timing of treatment

OBJECTIVE: To assess the accumulation of advanced glycation end products (AGEs) in streptozotocin (STZ)-induced diabetic rat cavernosal tissue, and to determine whether the protective effect of aminoguanidine (AG) on erectile function is related to the timing of treatment, as the accumulation of AGEs in the penis may be important in the pathogenesis of diabetes mellitus-induced erectile dysfunction, and prolonged treatment with AG (a selective AGE inhibitor), prevents erectile dysfunction in this situation. MATERIALS AND METHODS: Harlan Sprague-Dawley rats were divided into groups 1-4, i.e. age-matched controls; STZ diabetic rats (60 mg/kg intraperitoneal) given free access to water; STZ diabetic rats treated with AG (1 g/L per day in the drinking water) immediately after inducing diabetes; and STZ-diabetic rats treated with AG 1 month after inducing diabetes, respectively. Two months after inducing diabetes the intracavernosal pressure was measured after cavernosal nerve stimulation, and cavernosal AGE (5-hydroxy methyl furfural, 5-HMF) levels assessed. RESULTS: Cavernosal tissue 5-HMF levels from groups 2 and 4 were significantly higher than in group 1 (control). The expression of 5-HMF in group 3 was similar to that in group 1. Diabetic rats had significantly lower erectile function than controls, while groups 3 and 4 (treated with AG) had normal erectile function, as measured by cavernosal nerve stimulation. CONCLUSIONS: The effect of AG on AGE levels seems to be time-dependent; that the 1-month treatment with AG improved erectile function with no change in AGEs suggests that AG has protective effects on the penile vasculature through alternative pathways.     

The beneficial effect of clove essential oil and its major component,eugenol, on erectile function in diabetic rats

Diabetic men are at a higher risk of erectile dysfunction (ED). A tropical plant, clove (Syn. Eugenia caryophyllata, Caryophyllus aromaticus L., Syzygium aromaticum (L.) Merr. & L.M. Perry) from the Myrtaceae family has displayed aphrodisiac activity. The present research aimed to investigate the impacts of clove essential oil (CEO) and the ingredient of CEO, eugenol (E) on ED in diabetic rats. We divided Sprague-Dawley rats into control and diabetic groups. Erectile function was evaluated before and after CEO and E intracavernosal injection. CEO- and E-induced relaxation responses were investigated in isolated corpus cavernosum (CC) using various inhibitors. The intracavernous administration of CEO and E restored erectile responses in diabetic rats. CEO and E induced remarkable relaxation in all groups. CEO- and E-induced relaxation responses were partially inhibited after pre-contraction with KCl. Tetraethylammonium and glibenclamide inhibited the relaxation response to CEO. Glibenclamide inhibited maximum relaxation to E. The inhibitors of nitric oxide synthase (NOS), soluble guanylyl cyclase and nifedipine did not change CEO- and E-induced relaxation responses. The current results suggest that CEO and the major compound of the essential oil, E improved diabetes-induced ED in rats, and CEO caused CC relaxation via K⁺ channels independently NO signalling pathway.     

Effect of caffeine on erectile function via up-regulating cavernous cyclic guanosine monophosphate in diabetic rats

Erectile dysfunction (ED) is a common complication of diabetes mellitus. Phosphodiesterase-5 (PDE5) inhibitors, which inhibit the breakdown of intracellular cyclic guanosine monophosphate (cGMP), are used to treat diabetic ED. Caffeine, a nonselective PDE inhibitor used in our daily diet, is controversial regarding its effect on erectile function. To investigate the effect of caffeine on erectile function in diabetic rat models and explore the mechanism, male Sprague-Dawley rats were injected with streptozotocin to induce diabetes mellitus. The rats with blood glucose levels above 300 mg/dL were selected for the study. The rats were divided into 4 groups: group A (normal control rats), group B (diabetic rats treated with normal saline), group C (diabetic rats treated with caffeine, 10 mg/kg per day), and group D (diabetic rats treated with caffeine, 20 mg/kg per day). After 8 weeks of treatment, intracavernous pressure (ICP) was measured to assess erectile function. The radioimmunoassay was used to evaluate the level of cGMP in the cavernosum. The ICP and the cavernous cGMP decreased significantly in the diabetic rats compared with normal controls. An 8-week administration of caffeine at the given dosages increased the ICP and cavernous cGMP in diabetic rats. Caffeine consumption improved the erectile function of diabetic rats by up-regulating cavernous cGMP.     

Effect of sildenafil on platelet function and platelet cGMP of patients with erectile dysfunction

To investigate the effect of sildenafil on platelet function and cyclic guanosine monophosphate (cGMP) levels in patients with erectile dysfunction, we evaluated the association between erectile function and platelet responses after administration of 100 mg sildenafil. Erectile responses were monitored after 8 daily doses of the drug. Adenosine diphosphate (ADP) and collagen‐induced platelet aggregation and simultaneous adenosine triphosphate (ATP) release and cGMP levels were determined before and after sildenafil therapy. Basal levels for platelet aggregation, ATP release and cGMP were compared with age‐matched controls. There was no difference among basal levels of platelet responses between patients and controls, except for ADP‐induced platelet aggregation (P = 0.04). It was significantly higher in the patient group. Analysis of the responses to sildenafil revealed that for the patients who showed a positive erectile response, there was a significant increase in platelet cGMP (P = 0.028) and a decrease in ADP‐induced platelet aggregation (P = 0.04). However, for those who showed a negative or poor erectile response, there was no change in platelet cGMP levels and platelet functions. Sildenafil did not affect collagen‐induced platelet responses although cGMP levels of the responders increased. It is concluded that sildenafil increases platelet cGMP in the patients with positive erectile response. Therefore, it has been speculated that platelet cGMP may be used as an index for erectile response.     

糖尿病大鼠阴茎海绵体细胞凋亡的实验研究

目的 观察糖尿病(DM)大鼠阴茎海绵体细胞凋亡,探讨DM性阴茎勃起功能障碍(ED)的发病机理。方法 本文通过四氧嘧啶(Alloxan,AXN)诱导的DM大鼠模型,饲养8周后处死动物并取阴茎海绵体。用琼脂糖凝胶电泳法进行DNA片段分析;用TUNEL法检测细胞凋亡。结果 DM组DNA片段分析出现凋亡特征性梯带。DM组较对照组勃起组织凋亡细胞数明显增多(P<0.01)。结论 DM大鼠阴茎海绵体凋亡细胞增加,细胞凋亡可能是DM性ED的发病机理。