小檗碱对离体家兔阴茎海绵体cGMP和cAMP水平的影响

目的:观察小檗碱(berberine,Ber)对离体家兔阴茎海绵体平滑肌组织中环磷酸鸟苷(cGMP)和环磷酸腺苷(cAMP)水平的影响。方法:采用125I放射免疫测定法,以西地那非(sildenafil,Sil)为阳性对照,测定不同浓度的Ber对离体家兔阴茎海绵体平滑肌组织中cGMP和cAMP水平的影响。结果:Ber能直接升高cGMP的含量(P<0.05),EC50为1.75μmol/L,但对cAMP含量无显著影响。在cGMP激发剂硝普钠(SNP)存在下,Ber和Sil均能浓度依赖性地提高海绵体组织中cGMP浓度(P<0.01),促进cGMP生成的EC50分别为1.32、0.67μmol/L。同样的条件下,Ber和Sil对cAMP的浓度均无显著影响(P>0.05)。在cAMP激发剂前列腺素E1(PGE1)刺激下,Ber和Sil也能够提高海绵体组织中cAMP的浓度(P<0.01),表现出浓度依赖性,促进cAMP生成的EC50分别为4.90、6.53μmol/L。结论:Ber可提高阴茎海绵体平滑肌中cGMP、cAMP的浓度,此效应可能为其舒张阴茎海绵体的潜在机制。     

粉防己碱松弛离体新西兰白兔阴茎海绵体作用的研究

目的 :探讨粉防己碱 (Tet)对离体新西兰白兔阴茎海绵体的松弛作用。　方法 :采用离体新西兰白兔阴茎海绵体肌条张力记录法 ,观察Tet对氯化钾 (KCl)和去氧肾上腺素 (PE)诱导收缩的阴茎海绵体肌条的松弛作用 ;L 硝基精氨酸 (L NNA)和亚甲蓝处理后 ,Tet对PE诱导收缩的阴茎海绵体肌条松弛的作用。　结果 :10 μmol/L及3 0 μmol/L的Tet使KCl诱导的最大收缩反应分别降低为 ( 73 .0± 3 .8) %和 ( 41.5± 3 .4) % ,降低程度与Tet的浓度呈正比 (P <0 .0 1)。Tet对 10 μmol/LPE诱导的肌条收缩具有浓度依赖性松弛作用 ,1、10、3 0、10 0 μmol/L的Tet对PE诱导的阴茎海绵体肌条收缩的松弛效应分别为 ( 6.0± 1.4) %、( 2 1.3± 2 .2 ) %、( 47.4± 3 .3 ) %和 ( 68.1±3 .6) % (P <0 .0 1) ;而L NNA及亚甲蓝对Tet的松弛作用没有影响 (P >0 .0 5 )。　结论 :Tet能浓度依耐性地松弛离体新西兰白兔阴茎海绵体 ,其作用机制可能是通过阻滞钙通道 ,而与一氧化氮 环鸟苷酸 (NO cGMP)通路无关     

川芎嗪舒张离体兔阴茎海绵体平滑肌的作用及其机制的初步研究

目的 :探讨川芎嗪 (Chuanxiongzine ,Ligustrazine)对离体兔阴茎海绵体平滑肌条的舒张效应及其作用机制。　方法 :采用离体家兔阴茎海绵体肌条张力记录法 ,观察川芎嗪对去氧肾上腺素 (phenylephrine,PE)诱导收缩的阴茎海绵体肌条的舒张作用 ;应用亚硝基左旋精氨酸甲酯 (L NAME)、ODQ预处理和去除内皮 ,分别记录川芎嗪对阴茎海绵体肌的舒张作用。采用放射免疫法测定川芎嗪对阴茎海绵体平滑肌肌条中cGMP和cAMP含量的影响。　结果 :川芎嗪对阴茎海绵体平滑肌具有浓度依赖性舒张作用 ,其EC50 为 1 .5 8× 1 0 -4mol/L ,ODQ可部分抑制川芎嗪对肌条的舒张效应 (P <0 .0 5 ) ,而L NAME预处理和去除内皮对川芎嗪舒张肌条的效应没有影响 (P >0 .0 5 )。川芎嗪处理组阴茎海绵体平滑肌肌条中的cGMP和cAMP含量分别是对照组的 1 .5和 2 .3倍 ,差异有显著性 (P <0 .0 5 )。　结论 :川芎嗪对阴茎海绵体平滑肌具有浓度依赖性的舒张效应 ,其舒张作用机制与增加cGMP、cAMP浓度有关     

乙醇对离体家兔阴茎海绵体的松弛效应及其作用机制

目的:观察乙醇对离体家兔阴茎海绵体的效应并探讨其可能机制。方法:台式生理记录仪测定海绵体张力,放射免疫测定法测定阴茎海绵体cAMP和cGMP含量。结果:①1.25%(V/V)的乙醇能明显增强异丙肾上腺素(10-9～10-5mol/L)对海绵体肌条的舒张效应。②100、300μmol/L的腺苷酸环化酶抑制剂SQ22536能使乙醇(0.25%～3.5%,V/V)对去氧肾上腺素诱导收缩的肌条的舒张曲线右移,100、300μmol/LSQ22536分别使最大舒张效应由(105.12±3.39)%降低到(97.00±2.57)%和(91.09±2.42)%,EC50由(1.18±0.09)%分别增加到(1.36±0.10)%和(1.68±0.13)%(P均<0.05)。③乙醇可浓度依赖性增加家兔阴茎海绵体cAMP含量,而对cGMP含量无影响。④对于提取的兔离体海绵体组织细胞膜碎片上的腺苷酸环化酶,乙醇可浓度依赖性地增强其活性。结论:乙醇可舒张离体家兔海绵体平滑肌,其作用可能是通过cAMP信号转导通路实现的。     

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。     

不同月龄大鼠阴茎组织中内源性一氧化碳与环磷酸鸟苷和环磷酸腺苷的关系

目的:探讨增龄对大鼠阴茎组织中内源性一氧化碳(CO)与环磷酸鸟苷(cGMP)、环磷酸腺苷(cAMP)含量的变化。方法:8、16、24个月大鼠各8只,分别注射阿朴吗啡(APO)进行大鼠阴茎勃起功能实验;麻醉后取阴茎海绵体,用改良双波长分光光度法测量其CO浓度,并测量其cAPM、cGMP含量。结果:随月龄增加,CO含量降低,各月龄组间差异有显著性(P均<0.01);cGMP、cAMP含量均随月龄增加而逐渐下降,各月龄组间差异有显著性(P均<0.01)。结论:随月龄的增加,大鼠阴茎组织中CO、cAMP、cGMP含量下降,提示衰老对大鼠阴茎组织中CO、cAMP、cGMP含量影响显著。     

粉防己碱(Tet)对兔子阴茎海绵体平滑肌细胞质中自由钙离子浓度的影响(英文)

目的:探讨粉防己碱(tetrandrine,Tet)松弛阴茎海绵体平滑肌的作用机制。方法:体外培养新西兰白兔阴茎海绵体平滑肌细胞,经钙荧光指示剂 Fluo-2/AM 负载后,用荧光离子数字成像系统观察 Tet 对平滑肌细胞内[Ca~(2 )]_i 的影响。结果:Tet(1,10,100μmol/L)对平滑肌细胞内静息[Ca~(2 )]_i无明显影响(P>0.05)。当细胞外钙离子浓度为2.5 mmol/L 时,Tet(1μmol/L,10 μmol/L,100 μmol/L)抑制了高钾和去氧肾上腺素(PE)导致的细胞内[Ca~(2 )]_i 升高(P<0.05),这种抑制作用具有浓度依赖性。在无细胞外钙时,1 μmol/L和10μmol/L Tet 对 PE 引起的细胞内[Ca~(2 )]_i 升高无明显影响(P>0.05);而100 μmol/L Tet 能明显抑制 PE 引起的细胞内[Ca~(2 )]_i 升高(P<0.05)。结论:Tet 通过阻滞电压依赖性钙通道、α_1受体依赖性钙通道和抑制细胞内钙库释放,降低阴茎海绵体平滑肌细胞内[Ca~(2 )]_i 水平,这是 Tet 松弛阴茎海绵体平滑肌的作用机制之一。     

粉防己碱对新西兰白兔阴茎海绵体平滑肌细胞内游离钙离子浓度的影响

目的探讨粉防己碱(Tet)松弛阴茎海绵体平滑肌的作用机制。方法体外培养的第3～4代新西兰白兔阴茎海绵体平滑肌细胞,经钙荧光指示剂Fluo-2/AM负载后,用荧光离子数字成像系统观察Tet对平滑肌细胞内[Ca~(2 )]i的影响。结果Tet对平滑肌细胞内静息[Ca~(2 )]i无明显影响(P>0.05)。在细胞外钙浓度为2.5 mmol/L时,1、10和100μmol/LTet对高钾和去氧肾上腺素(PE)引起的细胞内[ca~(2 )]i升高有浓度依赖性地抑制作用。对40 mmol/L KCl引起的细胞内[Ca~(2 )]i升高的抑制率分别为22.0%、41.0%和73.0%(P<0.05)。对10μmol/L PE引起的细胞内[ca~(2 )]i升高的抑制率分别为15.0%、26.4%和46.6%(P<0.05)。在无细胞外钙时,1μmol/L和10μmol/L Tet对PE引起的细胞内[Ca~(2 )]i升高,无明显影响(P>0.05);而100μmol/L Tet能明显抑制PE引起的细胞内[ca~(2 )]i升高,抑制率为28.2%(P<0.05)。结论Tet可能通过阻滞电压依赖性钙通道、α1受体依赖性钙通道和抑制细胞内钙库释放,降低阴茎海绵体平滑肌细胞内[Ca~(2 )]i水平,这是Tet松弛阴茎海绵体平滑肌的作用机制之一。     

Rho激酶抑制剂法舒地尔改善高脂血症白兔阴茎勃起功能的实验研究

目的 研究Rho激酶抑制剂法舒地尔改善高脂血症新两兰白兔阴茎勃起功能的效应.方法 20只新西兰大白兔给予1%胆崮醇的高脂饲料连续喂养8周.喂养前检测血胆固醇浓度、体重、动脉血压和罂粟碱海绵体注射前后海绵体压力变化.喂养8周后再次检测上述指标.并应用0.75mg、1.5mg、3mg法舒地尔分别直接海绵体注射,检测动脉血压和海绵体压力变化情况.最后应用法舒地尔诱导离体高脂血症白兔阴茎海绵体平滑肌肌条舒张,并记录平滑肌肌张力的变化.结果 (1)高脂喂养后新西兰白兔的体重(2.42±0.24)kg及血总胆固醇水平(24.21±0.84)mmol/L均明显高于喂养前的体重(1.95±0.14)kg和血总胆固醇水平(3.22±0.15)mmol/L.(2)新西兰白兔经高脂饲料喂养后,罂粟碱导致阴茎海绵体内压较喂养前明显下降(7.83±2.51)mmHg Vs(19.81±3.69)mmHg.0.75mg、1.5mg、3mg法舒地尔海绵体内注射后,高脂血症白兔阴茎海绵体内压增高分别为(4.74±0.77)mmHg、(8.73±1.59)mmHg、(18.15±1.60)mmHg.(3)新西兰白兔经高脂饲料喂养后,离体阴茎平滑肌肌条在0.5 μmol、1.25 μmol、5 μmol、12.5 μmol、50 μmol和100 μmol剂量法舒地尔诱导下产生的舒张效应分别为(1.56±0.43) %、(5.03±1.02)%、(8.28±1.35)%、(16.77±3.57)%、(39.44±5.08)%和(61.87±4.85)%.结论 Rho激酶抑制剂法舒地尔能够有效改善高脂血症白兔的阴茎勃起功能.     

PDE5基因反义寡脱氧核苷酸对人阴茎海绵体平滑肌细胞cNMP的影响

目的 :观察PDE5基因反义寡脱氧核苷酸对人阴茎海绵体平滑肌细胞内cAMP和cGMP的影响 ,为阴茎勃起功能障碍的基因治疗提供理论和实验依据。　方法 :将PDE5基因反义寡脱氧核苷酸 (含第 1外显子部分序列 )与脂质转染试剂DOTAP共同转染人阴茎海绵体平滑肌原代细胞 ,以酶联免疫法分别检测转染后不同时间 (1～ 4 8h)海绵体平滑肌细胞内cAMP和cGMP的浓度变化 ,观察反义寡脱氧核苷酸对平滑肌细胞内cNMP的影响。　结果 :转染后 ,反义实验组平滑肌原代细胞内cGMP水平 (1～ 6h)显著高于对照组 (P <0 .0 1)。　结论 :PDE5基因反义寡脱氧核苷酸可以增加人阴茎海绵体平滑肌细胞cGMP水平 ,本研究有助于了解PDE5基因与cNMP在阴茎勃起中的作用 ,并为阴茎勃起功能障碍的基因治疗提供理论和实验基础。     

Intracellular mechanism of penile erection in monkeys

To elucidate the sequence of events between the release of neurotransmitters and cavernous smooth muscle relaxation in erection, we studied the role of the cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) systems. In a well-established simian model, the effects of specific agonists and antagonists of the intracellular sequence for smooth muscle relaxation and potassium channel openers on the intracavernous pressure were examined. Sodium nitroprusside (10^?3 M), a nitric oxide releaser and thus a stimulant of the cGMP system, caused an increase in the intracavernous pressure from 82 to 115 cm H₂O for 7 to 19 min and penile diameter from 24.8 ± 2.28 to 43 ± 4.87 mm. When nitroprusside was injected after methylene blue (10^?3 M), a specific antagonist of the enzyme guanylate cyclase, intracavernous pressure rise decreased significantly, but cromakalin, a potassium channel opener, provoked excellent increases after the block. A smaller dose of sodium nitroprusside (10^?4 M) caused an increase in intracavernous pressure from 35 to 85 cm H₂O for 7 to 11.5 min. When nitroprusside was injected after zaprinast, a phosphodiesterase inhibitor, the increase in pressure ranged from 80 to 116 cm H₂O for 15 to 30 min. Prostaglandin E₁, an activator of the cAMP system, caused an increase in the intracavernous pressure of 20–80 cm H₂O for 5 to 10 min, and an increase in penile diameter from 25 ± 2.22 to 35 ± 3.48 mm. The erectile response to PGE₁, but not to cromakalin, was nearly abolished by ethylmaleimide, an adenylate cyclase blocker. The response to nitroprusside was significantly greater (P < 0.05) than to PGE₁. Both systems. cAMP and cGMP, may be involved in cavernous smooth muscle relaxation, and cGMP is probably the predominant intracellular second messenger in penile erection in monkeys. Stimulants of the cGMP system, such as nitric oxide releasers, could represent a more physiological and effective approach in the treatment of erectile dysfunction. © 1994 Wiley-Liss, Inc.     

Effects of plant extract neferine on cyclic adenosine monophosphate and cyclic guanosine monophosphate levels in rabbit corpus cavernosum in vitro

Aim： To further investigate the relaxation mechanism of neferine （NED, a bis-benzylisoquinoline alkaloid extracted （isolated） from the green seed embryo of Nelumbo nucifera Gaertn in China, on rabbit corpus cavernosum tissue in vitro. Methods： The effects of Nef on the concentrations of cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP） in isolated and incubated rabbit corpus cavernosum tissue were recorded using ^125I radioimmunoassay. Results： The basal concentration of cAMP in corpus cavernosum tissue was 5.67 ± 0.97 pmol/mg. Nef increased the cAMP concentration in a dose-dependent manner （P 〈 0.05）, but this effect was not inhibited by an adenylate cyclase inhibitor （cis-N-[2-phenylcyclopentyl]azacyclotridec-1-en-2-amine, MDL-12, 330A） （P 〉 0.05）. The accumulation of cAMP induced by prostaglandin Et （PGEt, a stimulator of cAMP production） was also augmented by Nef in a dose-dependent manner （P 〈 0.05）. The basal concentration of cGMP in corpus cavernosum tissue is 0.44 ± 0.09 pmol/mg. Nef did not affect this concentration of cGMP, either in the presence or in the absence of a guanyl cyclase inhibitor （1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, ODQ） （P 〉 0.05）. Also, sodium nitroprusside （SNP, a stimulator of cGMP production）-induced cGMP production was not enhanced by Nef （P 〉 0.05）. Conclusion： Nef, with its relaxation mechanism, can enhance the concentration of cAMP in rabbit corpus cavernosum tissue, probably by inhibiting phosphodiesterase activity. （Asian JAndro12008 Mar; 10： 307-312）     

RETRACTED ARTICLE: Dibutyryl cyclic AMP increases the contractility of fatigued diaphragm in dogs

The effects of dibutyryl cyclic AMP (DBcAMP) on the contractility of nonfatigued and fatigued diaphragms were studied in 36 anesthetized and mechanically ventilated dogs. The animals were divided into four groups. In group C₁ (n=8), dogs without fatigue received only Ringer's lactate solution. In group D₁ (n=8), dogs without fatigue were given a continuous infusion of DBcAMP 0.2 mg·kg⁻¹·min⁻¹. In groups C₂ and D₂ (n=10 each), diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied for 30 min. In group D₂, after producing fatigue, DBcAMP 0.2 mg·kg⁻¹·min⁻¹ was administered. In groups C₂, only Ringer's solution was administered during this period. Diaphragmatic contractility was assessed by measuring the transdiaphragmatic pressure (P_di, cmH₂O). No difference in P_di was observed in groups C₁ and D₁. After diaphragmatic fatigue in groups C₂ and D₂, P_di at low-frequency (20-Hz) stimulation decreased significantly compared with the prefatigue values (group C₂; 9.3±1.9vs 12.5±2.4, group D₂; 9.3±2.1vs 12.5±2.6; mean±SD;P<0.05), whereas no change in P_di was observed at high-frequency (100-Hz) stimulation. In group D₂, P_di at both stimuli increased significantly with an infusion of DBcAMP compared with the fatigue values (20 Hz; 13.3±3.3vs 9.3±2.1, 100 Hz; 23.4±3.6vs 21.3±3.2;P<0.05). In group C₂, the speed of recovery from fatigue was relatively slower at 20-Hz stimulation than at 100-Hz stimulation. It is concluded that DBcAMP increases the contractility of fatigued diaphragm, but that this agent does not affect the contractility of nonfatigued diaphragm.     

Cyclic Nucleotides in Rat Brain During Lidocaine Infusion

The concentrations of cyclic 3', 5'-guanosine monophosphate (cGMP) and cyclic 3', 5'-adenosine monophosphate (cAMP) in the cerebellar and cerebral cortex were measured during lidocaine infusion and during bicuculline-induced seizures in rats. The rats were divided into three groups: control, lidocaine (0.74 mg/min) and bicuculline (1.2 mg/kg). The lidocaine group was divided into four stages according to the EEG pattern; desynchronized, synchronized, seizure and recovery. At the desynchronized and synchronized stages, cGMP and cAMP concentrations in both cerebellar and cerebral cortex remained unchanged except for a modest decrease in cerebral cGMP at the desynchronized stage. At the seizure stage, cerebellar cGMP increased from 5.2 +/- 0.9 to 9.2 +/- 1.4 pmol/mg protein and cerebellar cAMP decreased from 8.9 +/- 0.6 to 6.9 +/- 0.6 pmol/mg protein. These changes in concentrations at the seizure stage returned to the control at the recovery stage. During bicuculline-induced seizures, cGMP and cAMP concentrations increased strikingly in both cerebellar and cerebral cortex. These results indicated that lidocaine-induced seizures were accompanied by significant changes in cerebellar cyclic nucleotide concentrations in rats.     

Natriuresis and cyclic GMP stimulation by parathyroid hormone 1-34 in man

Synthetic human parathyroid hormone (PTH 1-34) was infused into seven healthy adults and their renal responsiveness examined. Blood and urine were collected at time zero and at 30 and 60 min after the infusion of PTH 1-34 (15μg in 50 ml of glucose solution infused in 10 min). A highly significant and parallel rise in both cyclic GMP and sodium excretion was found. No variation in blood atrial natriuretic factor concentration could be detected thereby suggesting that cyclic GMP is directly stimulated by PTH 1-34 and may play a role in the natriuretic effect of PTH.     

膀胱过度活动症大鼠膀胱及脊髓背根节中HCN4离子通道蛋白的表达

目的检测超极化激活环核苷酸门控阳离子通道4(HCN4)蛋白在膀胱过度活动症(OAB)模型大鼠膀胱及脊髓背根节(DRG)中的表达变化。方法①成年雌性SD大鼠(240~260g)随机分为OAB-4周、OAB-6周、OAB-8周(每组10只)和对照组(10只):采用尿道近端结扎法,建立膀胱出口梗阻(BOO)诱导的OAB动物模型。②建模后4、6、8周行尿流动力学检测,筛选OAB动物。③应用Western blot等方法检测对照组及OAB模型不同时间点大鼠膀胱黏膜层及肌层内HCN4通道蛋白的表达变化,并检测上述不同处理组大鼠膀胱对应脊髓背根节(DRG)中HCN4蛋白表达情况。结果膀胱尿动力学检测结果提示:OAB组膀胱逼尿肌自发性收缩频率随时间明显升高,且8周组明显高于4周及6周组。Western blot检测显示,HCN4通道蛋白在对照组及OAB组均有表达,与对照组相比,OAB组的膀胱黏膜层及肌层中HCN4蛋白表达量随OAB发生时间均显著增高(P0.01),在OAB-8周组达到最高。DRG组织中HCN4通道蛋白随OAB发生时间显著增高(P0.01),且OAB-8周组表达量最高。结论 HCN4通道在大鼠膀胱黏膜层、肌层以及膀胱对应脊髓DRG中均有表达,且OAB组较对照组显著增多,并随OAB发生时间而升高。提示HCN4通道可能参与了OAB膀胱功能的可塑性变化。     

Influences of dibutyryl cyclic adenosine monophosphate and forskolin on human sperm motility in vitro

Aim: To study the influences of dibutyryl cyclic adenosine monophosphate (dbcAMP) and forskolin on human sperm motility in vitro. Methods: Semen samples, aseptically obtained by masturbation and prepared by swim-up technique from 20 fertile men, were incubated with different concenlrations of dbcAMP and forskolin at 37℃. Measurements were carried out after l0 min, 20 min, 30 min and 60 min incubation. Motility parameters were estimated by using an automatic analyzing system. Results: Treatment with dbcAMP or forskolin resulted in a significant increase in sperm motility and progressive motility. The larger the concenlrations of dbcAMP or forskolin,the greater the effect appeared. The straight linear velocity and curvilinear velocity were not affected by both agents.Conclusion: dbcAMP and forskolin increase the motility and progressive motility of human sperm in vitro. ( Asian J Androl 2003 Jun; 5: 113-115)     

Effect of the potassium-channel opener nicorandil as an adjunct to cardioplegia on myocardial preservation in isolated rabbit hearts

We studied the effect of nicorandil on the hemodynamic, biochemical, and ultrastructural changes in rabbit hearts (n=50) rendered cardioplegic with a single injection of Bretschneider's HTK solution over 30min or 60min at 37°C or 15°C, followed by reperfusion at 37°C for 60min. Particular attention was focused on the aspects of doseresponse relationship, temperature sensitivity, and ischemic tolerance. Isolated hearts were prepared for modified Langendorff circulation using modified Krebs-Henseleit bicarbonate solution bubbled with a 95% O₂-5% CO₂ gas mixture, to which nicorandil (0, 0.1, 1, and 5 mM) was added. The optimal concentration of nicroandil was 1 mM, which increased the recovery of left ventricular (LV) function, affecting coronary flow and the myocardial cyclic adenosine monophosphate, but not the myocardial concentrations of adenine nucleotide compounds or total calcium. These effects were abolished by the addition of glibenclamide to the HTK, but they were not diminished by a high potassium (K⁺) concentration of 20 mM. The addition of nicorandil 1 mM to the HTK at 15°C did not improve the recovery of LV function. Our result suggested that nicorandil used adjunctly prevents LV functional depression after 30 min, and possibly 60 min of cardioplegia at 37°C, and that this effect is not disturbed by a high K⁺ concentration up to 20 mM. However, nicorandil has temperature sensitivity whereby it loses its efficacy at 15°C.     

Possible role of human growth hormone in penile erection

PURPOSE: Treatment with recombinant human growth hormone in adult patients with growth hormone deficiency increases nitric oxide and cyclic guanosine monophosphate (cGMP). We examined the functional in vitro effects of recombinant human growth hormone on tissue tension and cyclic nucleotide levels of human corpus cavernosum and detected changes in growth hormone in the cavernous and peripheral blood during different phases of penile erection. MATERIALS AND METHODS: Relaxant responses of human corpus cavernosum were investigated using the organ bath technique. Tissue levels of cGMP were determined by a specific radioimmunoassay after dose dependent exposition of isolated human corpus cavernosum strips to recombinant human growth hormone. In 35 healthy potent volunteers blood samples were obtained simultaneously from the corpus cavernosum and cubital vein during different functional conditions of the penis, including flaccidity, tumescence, rigidity and detumescence. Penile erection was induced by audiovisual and tactile stimulation. Serum growth hormone was determined by an immunoradiometric assay. RESULTS: Recombinant human growth hormone elicited dose dependent relaxation of human corpus cavernosum strips in vitro. The relaxing potency of recombinant human growth hormone was paralleled by its ability to elevate intracellular levels of cGMP. In vivo the peripheral growth hormone serum profile of the respective penile conditions did not significantly differ from those of cavernous serum. The main increase in growth hormone to greater than 90% was determined during developing penile tumescence, followed by a transient decrease afterward. CONCLUSIONS: These results suggest that penile erection may probably be induced by growth hormone through its cGMP stimulating activity on human corpus cavernosum smooth muscle.     

不同应力条件对体外培养成肌细胞命运的影响

目的：探讨对体外培养成肌细胞施加不同牵张应力后细胞命运的改变,为临床合理施加矫形力提供理论依据。方法：利用Flexer cell细胞加力仪器与弹性加力板对体外培养C2C12成肌细胞施加不同频率、幅度的牵张应力,形变量代表应力幅度。通过MTT实验和PARP剪切实验测定在受到不同大小的牵张应力作用下（0%,5%,10%,15%,20%/10 cycles/min）的C2C12细胞的增殖和凋亡情况,通过检测细胞分化相关基因的表达改变,分析应力条件下细胞分化状态的改变。结果：5%的周期性应力可以促进细胞的增殖,同时抑制分化培养基诱导的细胞分化相关基因myogenin等的表达。当牵张应力大于10%后,可以观察到明显的DNA断裂。除此以外,我们还发现牵张应力大于10%后,细胞内开始出现大量的PARP剪切产物,随应力的增加而增多。当周期性牵张应力超过15%10cycles/min时,整体存活细胞数明显降低。结论：高强度牵拉介导的细胞凋亡,参与整体细胞数的减少,可能不利于组织的重塑和再生。