Stimulating effects of alanine and glycine on guinea-pig taenia coli (author's transl)]

Effects of alanine and glycine on the mechanical and electrical activities of guinea-pig taenia coli were investigated. Alanine (0.1--10 mM) and glycine (0.5--10 mM) produced a dose dependent contraction of guinea-pig taenia coli. The stimulating effects of alanine and glycine were not inhibited in the presence of atropine (5 muM), tetrodotoxin (0.1 micrograms/ml), diphenhydramine (4 muM), methysergide (3 muM), strychnine (10 muM), and were not influenced by treatment with indomethacin (3 muM). However, these effects were inhibited in the presence of a Ca antagonist, verapamil (10 muM). When the electrical activities of the taenia coli were recorded by the single sucrose-gap method, alanine and glycine (5--10 mM) produced a reduction of membrane potential and increased spike heights and frequencies of action potential. In LiCl or Choline-Cl and in Na-isethionate solutions, the stimulating effect of alanine was not abolished, but was completely inhibited in KCl-depolarized preparation. From these results, it is considered that both alanine and glycine may directly produce contraction by a depolarization of the cell membrane of guinea-pig taenia coli.     

Effects of sodium vanadate on the smooth muscle of the guinea-pig vas deferens

Effects of sodium vanadate on electrical and mechanical activities of smooth muscle of the guinea-pig vas deferens were investigated. Sodium vanadate of concentrations higher than 5 X 10(-6) M caused an elevation of basal tension and, at concentrations higher than 5 X 10(-4) M, initiated spontaneous contractions. These effects were not blocked by treatments with reserpine, tetrodotoxin or phentolamine. Treatment with ouabain also did not block the tension development by sodium vanadate. Sodium vanadate caused slight depolarization of membrane and potentiated spike activities. The phasic contraction of potassium contracture was potentiated by sodium vanadate in a similar manner to pretreatment with 15 mM K+ or with ouabain, both treatments occasioning slight depolarization. Sodium vanadate also caused tension development in K-depolarized preparetions. Contrastingly, drug-induced contractions were not significantly affected by sodium vanadate. It is suggested that sodium vanadate acts directly on smooth muscles and causes tension development without relation to Na, K-ATPase activity. Changes in the membrane electrical activities may be part of the cause of contraction. However, it can also initiate tension development without membrane potential changes, presumably acting on intracellular Ca binding sites.     

Contraction independent of extracellular Ca by sodium vanadate in guinea-pig vas deferens

The effects of Ca removal and Ca antagonists on sodium vanadate-induced contractions of the guinea-pig vas deferens were studied. Sodium vanadate-induced tension development could be observed even 120 minutes after the removal of Ca, whereas K-contracture disappeared within 20 minutes. Spontaneous contractions induced by sodium vanadate were abolished by the removal of Ca. Verapamil and nifedipine did not show any effect on sodium vanadate-induced contraction, contrastingly, they blocked spontaneous contractions initiated by sodium vanadate. The effects of sodium vanadate on Ca contracture of depolarized preparations were also studied. Though the drug potentiated phasic contraction, it did not potentiate tonic component of Ca contracture. It was demonstrated that sodium vanadate induced tension development independently of extracellular Ca, presumably by releasing intracellularly bound Ca.     

Sodium nitroprusside as a coronary vasodilator in man: a comparison of the effects of sodium nitroprusside and papaverine hydrochloride on aortocoronary saphenous vein graft flow.

Blood flow in aortocoronary saphenous vein grafts was studied in response to intragraft injection of sodium nitroprusside and papaverine hydrochloride. Following injection of 50 mug of sodium nitroprusside, mean graft flow increased from 40.1 +/- 4.5 to 81.3 +/- 8.5 ml per minute. Administration of 30 mg of papaverine hydrochloride caused mean graft flow to rise from 35.4 +/- 3.9 to 70 +/- 7.9 ml per minute. Sodium nitroprusside increases aortocoronary graft flow, the doubling effect of 50 mug of the drug being of the same order of magnitude as that induced by 30 mg of papaverine hydrochloride.     

The effects of vasectomy on the autonomic innervation of the human vas deferens

Neurohistochemical and fine structural techniques have been employed to examine the intramural autonomic innervation of the human vas deferens following surgical division of the duct one to 15 years previously. Samples from sites on the distal (testicular) and proximal (urethral) aspects of the original vasectomy have been compared with control specimens obtained at vasectomy as to the arrangement and distribution of autonomic nerves. In contrast with tissue from the proximal part and from controls, the distal samples revealed a marked reduction in the noradrenergic innervation of the muscle coat. In addition acetylcholinesterase-containing nerves associated with the basal aspect of the epithelium were usually absent from the distal portion of the vas deferens. These findings have been considered in relation to the contractile and secretory activities of the organ following vasovasostomy and may be of importance to the maturation and fertility of spermatozoa.     

A comparison of the endocrine effects of hypotension induced by nicardipine with those by sodium nitroprusside in dogs

Plasma catecholamines, plasma renin activity, plasma aldosterone and plasma cortisol during hypotension induced by sodium nitroprusside and nicardipine were studied in 27 mongrel dogs under 0.87% halothane in oxygen. They were randomly divided into three groups: sodium nitroprusside (group S: n = 8), nicardipine (group N: n = 8) and controls (group C: n = 9). Group C received no vasodilator therapy and served as a control. Mean arterial pressure was reduced and maintained at 60 mmHg for 60 minutes in hypotensive groups. No changes were noted in plasma catecholamines and plasma cortisol in group C throughout the experiment, but plasma renin activity and plasma aldosterone decreased progressively. During hypotension induced by sodium nitroprusside and nicardipine, plasma epinephrine was significantly higher than the control value. However, after the hypotensive drugs were discontinued, plasma epinephrine decreased slightly. During and after induced hypotension, plasma renin activity of group N and group S were significantly higher than the control values. The highest levels of plasma renin activity 36.7 ng.ml-1.hr-1 in group N and 23.2 ng.ml-1.hr-1 in group S were observed. Plasma aldosterone concentration was significantly higher than the control value in group N. The maximum increase occurred 30 minutes after discontinuation of the nicardipine and the highest concentration of plasma aldosterone was three times control value. In contrast, in group S, plasma aldosterone was unchanged from the control value. Plasma cortisol concentration of group N was significantly increased than the control value. However, in group S, plasma cortisol concentration showed a slight but not significant increase.(ABSTRACT TRUNCATED AT 250 WORDS)     

SNP对生殖细胞凋亡作用的研究

目的探讨一氧化氮(NO)供体硝普钠(SNP)对大鼠睾丸生殖细胞凋亡的影响。方法采用末端脱氧核苷酸转移酶(TdT)介导的原位末端标记法(TUNEL),透射电镜和琼脂糖凝胶电泳检测生殖细胞凋亡的特征。结果TUNEL标记法检测表明,NO供体SNP可诱导生殖细胞的凋亡,并呈剂量时间依赖性,SNP组凋亡率明显高于对照组(P＜0.01)。透射电镜观察SNP处理15～20h后的生殖细胞,核染色质凝集,附着于核边缘呈新月形,核固缩、碎裂形成凋亡小体。琼脂糖凝胶电泳显示生殖细胞DNA片段呈现凋亡特征性的梯形区带。结论一氧化氮对生殖细胞的凋亡具有促使形成作用,这对不育症的研究有重要的价值。     

Hemodynamic and sympathetic effects of fenoldopam and sodium nitroprusside

BACKGROUND: Fenoldopam is a novel dopamine-1 receptor selective agonist that can be used as a vasodilator perioperatively to treat hypertension and to produce induced hypotension. We were interested to find out whether there were any differences between fenoldopam (FM) and sodium nitroprusside (SNP), one of the most popular vasodilators, in their effects on hemodynamics and sympathetic outflow using not only neuraxis intact but also baro-denervated animal models. METHODS: A total of 60 New Zealand white rabbits were divided into two groups of 30 each: the neuraxis-intact group and the totally baro-denervated group. Each group was further divided into three groups of 10 each to receive SNP 10 microg x kg(-1), FM 10 microg x kg(-1) or FM 20 microg x kg(-1), respectively. Mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were recorded before and after intravenous (i.v.) administration of each agent. In addition, cardiac and sympathetic baroreflex sensitivity were assessed in the neuraxis-intact animals. RESULTS: In the neuraxis-intact groups, although RSNA was increased to a similar extent in all three groups (P<0.01), the reduction of MAP with FM groups was significantly greater than with SNP (P<0.05). HR was increased only in the SNP group. Cardiac (HR) and sympathetic barosensitivity were significantly attenuated with FM 20 microg x kg(-1) as compared to the SNP group. In the baro-denervated groups, there were significant and similar degrees of reduction of MAP in all three group up to 1 min (P<0.01). MAP remained significantly decreased in the FM groups for 10 min (only 2 min with SNP) in both animal models. CONCLUSIONS: Unlike sodium nitroprusside, fenoldopam attenuates both cardiac (heart rate) and sympathetic baroreflex sensitivity, which may explain the lack of rebound hypertension with fenoldopam. The offset of hypotensive effects of fenoldopam is a significantly slower process as compared to nitroprusside, and this may be an unfavorable feature of fenoldopam should overshoot of hypotension occur.     

Aperistalsis of the vas deferens corrected with administration of ephedrine

An infertile patient with azoospermia, normal spermatogenesis on a testis biopsy and no sperm seen on a post-ejaculate urinalysis underwent bilateral scrotal exploration. Normal anatomy was found at exploration and bilateral vasograms demonstrated the absence of obstruction. After subsequent therapy with ephedrine semen analysis showed a total sperm count of 72 million.     

The actions of sodium nitroprusside and the phosphodiesterase inhibitor dipyridamole on phasic activity in the isolated guinea-pig bladder

OBJECTIVE: To investigate the actions of the nitric oxide (NO) donor sodium nitroprusside (SNP) and phosphodiesterase (PDE) inhibitors, which purport to affect intracellular cGMP levels, on the phasic activity generated by agonist stimulation of the isolated whole bladder of the guinea pig. MATERIALS AND METHODS: Isolated whole bladders from female guinea pigs (270-300 g) were used in all experiments. Each bladder was cannulated via the urethra and suspended in a chamber containing oxygenated solution at 33-35 degrees C. Bladder pressure was recorded and pharmacological agents added to the solution bathing the abluminal surface of the bladder. RESULTS: In the unstimulated bladder, SNP at up to 300 micromol/L caused only small (<2 cmH(2)O) rises in intravesical pressure. In the presence of phasic activity induced by either muscarinic or nicotinic stimulation, SNP at > 30 micromol/L, produced a dose-dependent increase in the frequency of the transients. The cells responding to SNP with an increase in intracellular cGMP were identified by immunofluorescence, and were in the suburothelial layer and within the muscle bundles. Smooth muscle cells of the detrusor body did not show a rise in cGMP. Exposure to the cGMP/PDE inhibitor zaprinast had no effect on phasic activity, but exposure to dipyridamole produced a transient rise in frequency, followed by an inhibition. Dipyridamole also significantly increased the amplitude of the phasic activity. CONCLUSION: These data show an excitatory role for NO/cGMP in the integrated regulation of phasic bladder activity. One population of cells which may be involved may be in the suburothelial layer and within the muscles. The differential sensitivity to PDE inhibitors affecting cGMP suggests that the cells responsible express specific isoforms of these regulatory enzymes. The importance of these observations, their possible role in the integrated physiology of the bladder and origins of bladder pathology, are discussed.     

Inhibition by cyclopropane of release od norepinephrine, but not dopamine-beta-hydroxylase, from the guinea-pig vas deferens.

Like halothane, cyclopropane reduces stimulation-induced release of norepinephrine, but not release of dopamine-beta-hydroxylase, from the isolated guinea-pig vas deverens. The dissociation between transmitter release and enzyme release in the presence of cyclopropane may be the result of either an increase in the affinity of norepinephrine for binding sites on the vesicular membrane produced by cyclopropane, or a direct effect of cyclopropane on a mechanism of release of norepinephrine that could be controlled independently of release of dopamine-beta-hydroxylase.     

Rat auxiliary liver transplantation without portal vein reconstruction: comparison with the portal vein-arterialized model

Auxiliary liver transplantation (ALT) has been reintroduced in clinical cases recently and is now believed to be a viable alternative to orthotopic liver transplantation. To provide a simple rat ALT model for studying the physiological and immunological aspects of the ALT graft, a new ALT was performed, and the comparison between this new model and the portal arterialized one that was reported by other investigators was carried out. At first, we confirmed that liver could tolerate the deprivation of its portal flow well, using a portosystemic shunted rat model. The new rat ALT model, in which the ALT graft obtained its blood inflow only from the hepatic artery, was then performed. Our results demonstrated that 50% of the hepatic artery-alone ALT graft showed almost normal structure histologically at 1 month after grafting, with bile secretion preserved. By contrast, only 8% 1-month graft survival was noted in the portal arterialized group, and all grafts stopped bile secretion 1 week after operation. In conclusion, with arterial blood supply alone, the ALT graft survived and demonstrated normal bile secretion function for more than 1 month. Portal vein arterialization is not an appropriate way to establish the graft's blood supply if no pressure adjustment measures were taken in advance.     

Expression of the p63 and Notch signaling systems in rat testes during postnatal development: comparison with their expression levels in the epididymis and vas deferens

The role of tubular structures that contribute to the passage of spermatozoa is not solely passive; these structures actively contribute to their own functions, although these tubules and ducts are contiguous and collaborate in the development of the male gamete along their lengths. The testis has the specific function to generate spermatozoa and spermatozoa undergo numerous changes as they pass through the epididymis. A member of the p53 family of genes, p63, is highly expressed in the basal layers of epithelial tissues and plays a key role in maintaining their cell populations, whereas Notch 1 and its ligand Jagged 2 have an important role in the differentiation of germ cells and Jagged 2 is up-regulated by TAp63, one of the p63 isoforms, which transactivates p53 target genes and induces apoptosis. Although the presence of p63 in most epithelia is established, the role of p63 and its possible relationship with the Notch system in the seminiferous epithelium have not been examined. Therefore, we investigated the expression of p63, Jagged 2, and Notch 1 in the testis during postnatal development in comparison with their expression levels in the vaso-epididymal epithelium. In the testis, the expression of TAp63 mRNA increased at day 14 after birth and the expressions of Jagged 2 and Notch 1 mRNA increased at day 16 after birth, suggesting that TAp63-mediated Jagged 2 induction activates the Notch signaling system. On the other hand, the strong signal of DeltaNp63 mRNA was already recognized in the vas deferens at day 0 after birth and advanced chronologically along the duct to the caput epididymis and p63 protein was expressed in basal cells in their epithelium, whereas the mRNAs of Jagged 2 and Notch 1 were maintained at a low level. Consequently, examination of our data raises the probability that TAp63 has an important role for maintenance of germ cell numbers, triggering or balancing the development, differentiation, and apoptosis of germ cells in the testis, which is completely different from the role of DeltaNp63 in other epithelial tissues.     

Hormonal influence on the neurogenic response of the hamster vas deferens

The effect of castration on in vitro contractility of smooth muscle of the vas deferens and body of the bladder has been studied in the hamster. Castration produced supersensitivity to in vitro electrical stimulation and norepinephrine in the vas deferens, but had no effect on the body of the bladder. Castration also increased the maximum contractile response of the vas deferens to electrical stimulation, norepinephrine, ATP, acetylcholine and histamine. The changes in contractility of smooth muscle of the vas deferens developed slowly and may be explained by specific effects upon adrenergic and purinergic neurotransmission and/or non-specific effects upon smooth muscle cell membranes.     

Immunoreactive arginine vasopressin (AVP) and effects of AVP in the human vas deferens

Immunoreactive (IR) arginine vasopressin (AVP) was found to occur in the epididymal part of the human vas deferens. Segments from nine different subjects all contained IR-AVP in concentrations ranging from 37 to 717 fmol/gm. wet weight, concentrations severalfold higher than those normally found in the circulation. IR-AVP was shown by high performance liquid chromatography to elute in the same position as synthetic AVP. AVP added to isolated preparations of the human vas deferens induced concentration-related repetitive phasic contractions without significant changes of baseline tension. These contractions seemed to be mediated via stimulation of vasopressin V1-receptors and were abolished in the presence of vasopressin antagonists. Contractions induced by electrical field stimulation were frequency-dependent and sensitive to tetrodotoxin and prazosin. They were not affected by the vasopressin antagonists used. AVP increased the response to electrical field stimulation and this effect was inhibited by vasopressin antagonists. The results suggest either that circulating AVP is taken up and accumulated by the human vas deferens, and/or that AVP is synthesized locally. They do not suggest co-release of AVP and noradrenaline from nerve endings. The physiological role of the AVP occurring in the human vas deferens remains to be established.