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At least 307 records · Page 17Linked to original sources
PubMed2006

Uroselectivity in male dogs of silodosin (KMD-3213), a novel drug for the obstructive component of benign prostatic hyperplasia.

AIMS: Our main aim was to compare the prostatic selectivity of silodosin with that of other alpha(1)-adrenoceptor (AR) antagonists. METHODS: We examined uroselectivities in two sets of experiments namely, in vitro and in vivo functional studies using male dogs. In the in vitro study, after evaluating the inhibitory effects of silodosin on noradrenaline (NA)-induced contractions in the isolated prostate and isolated carotid artery using the Magnus method, we calculated prostatic selectivity. In the in vivo study, we examined the effects of drugs on the hypogastric nerve stimulation (HNS)-induced increase in intraurethral pressure (IUP) and on blood pressure. The uroselectivity of silodosin was compared with those of tamsulosin and naftopidil. RESULTS: In vitro, all drugs antagonized NA-induced contraction in both prostate and carotid artery. The prostatic selectivity of silodosin (79.4) was much higher than those of tamsulosin (1.78), naftopidil (0.55), BMY 7378 (0.115), and prazosin (0.01). In vivo, intravenously (i.v.) administered silodosin dose-dependently inhibited the HNS-induced increase in IUP with much less hypotensive effect than either tamsulosin or naftopidil, the uroselectivity (ED(15)/ID(50)) of silodosin (237) being significantly higher than those of tamsulosin (1.21) and naftopidil (2.65). CONCLUSIONS: Our results clearly demonstrate that silodosin is a potent and highly selective alpha(1A)-AR antagonist. A selective alpha(1A)-AR antagonist such as silodosin may have good potential as a less-hypotensive drug for the treatment of urinary dysfunction in benign prostatic hyperplasia patients.

Adrenergic alpha-1 Receptor Agonists↗
PubMed2000

Lateral ligament: its anatomy and clinical importance.

Since Miles proposed abdominoperineal excision as a radical surgery for rectal cancer in 1908, surgeons have recognized the lateral ligament in the pararectal space of their patients and attached clinical importance to it, although anatomists did not describe any such configuration in cadavers. By analyzing an experience of 421 lower rectal cancer cases at the Cancer Institute Hospital in Tokyo, discussion of the lateral ligament was focused on its relationship to the fascial arrangements in the pelvis, the pelvic autonomic nervous system, and the lymphatic drainage of the rectum. The lateral ligament is not an anatomical term, but a clinical or surgical one. It exists in a living pelvis as a condensation of connective tissue around the middle rectal artery and is divided into two segments by the inferior hypogastric nerve plexus inside it and the visceral endopelvic fascia around it. The lateral ligament is a pathway of blood vessels and nerve fibers toward the rectum and lymphatic vessels from the lower rectum toward the iliac lymph nodes. Therefore, the lateral ligament plays a critical role in surgery for lower rectal cancer in two respects: the anatomic extent of resection for curing rectal cancer, and the preservation of sexual function.

Collateral Ligaments↗
PubMed1988

Substance P-mediated membrane currents in voltage-clamped guinea pig inferior mesenteric ganglion cells.

Responses to substance P (SP) and to hypogastric nerve stimulation were recorded from voltage-clamped guinea pig inferior mesenteric ganglion (IMG) neurons, and compared with those to muscarine. Muscarine produced a voltage-dependent inward current accompanied by a reduced input conductance and inhibition of IM a time- and voltage-dependent K+-current (Brown and Adams: Nature 283:673-676, 1980). SP also produced an inward current, accompanied by a fall in input conductance (20 out of 31 cells) or a rise in input conductance (7 out of 31 cells). The fall in input conductance was not accompanied by an inhibition of M-current (unlike frog ganglia: Adams et al.: British Journal of Pharmacology 79:330-333, 1983) or an inhibition of the inward rectifier current (unlike globus pallidus neurons: Stanfield et al.: Nature 315:498-501, 1985). Repetitive hypogastric nerve stimulation (10-20 Hz, 2-10 s) produced a slow inward postsynaptic current lasting 1-3 min, with decreases or increases of input conductance matching those produced by SP. The postsynaptic current did not show a consistent or reproducible change in amplitude on varying the holding potential between -90 and -25 mV. It is concluded that SP and hypogastric stimulation produce complex and variable changes in ionic conductance in IMG neurons.

Animals↗
PubMed1990

Differential distribution in, and release from, sympathetic nerve endings of endogenous noradrenaline and recently incorporated catecholamines.

Guinea-pig vasa deferentia or hypogastric nerve-vas deferens preparations, preincubated with pargyline (to irreversibly inhibit monoamine oxidase), were exposed to 2.3 mumol/l of unlabelled adrenaline or of 3H-7-(-)-noradrenaline in the presence of hydrocortisone (to inhibit extraneuronal uptake). The vasa deferentia were then mounted in perifusion chambers and subjected to transmural electrical stimulation, electrical stimulation of the nerve, depolarization by potassium (50 mmol/l), or addition of tyramine (40 mumol/l). The evoked overflow of tritium and of unlabelled catecholamines was expressed as a fraction of their tissue content. For all stimuli, the fractional release of the exogenous amines was higher than that of endogenous noradrenaline. Thus, recently incorporated amines are preferentially mobilized irrespective of the particular type of releasing mechanism or the chemical nature of the amine. In vasa deferentia which had been loaded with increasing amounts of adrenaline (by incubating the tissues with adrenaline at concentrations ranging from 0.6 to 160 mumol/l), the fractional release of adrenaline decreased and became closer to that of endogenous noradrenaline. Hence, the access of exogenous catecholamines to the deepest storage sites requires higher concentrations of amines than those needed to reach the more easily releasable pools. Light microscope autoradiographs obtained from slices of vasa deferentia previously loaded with 2.3 mumol/l 3H-(-)-noradrenaline showed that the outer layers were strongly labelled with silver grains whereas the inner layers were poorly marked. It is concluded that recently incorporated amines are preferentially stored in varicosities close to the surface of the tissue and, in comparison with endogenous noradrenaline, are preferentially released from sympathetically innervated organs.

Animals↗
PubMed1995

Comparison of corelease of noradrenaline and ATP evoked by hypogastric nerve stimulation and field stimulation in guinea-pig vas deferens.

Contractions and overflow of tritium and ATP elicited by hypogastric nerve stimulation (HNS) and field stimulation (FS) were studied in the guinea-pig isolated vas deferens preincubated with [3H]-noradrenaline. ATP was measured by means of the luciferin-luciferase technique. HNS and FS elicited contraction, tritium overflow and ATP overflow. HNS at supramaximal current strength produced smaller responses than did FS at supramaximal current strength (210 pulses/7 Hz). Supramaximal HNS and submaximal FS were used in the remainder of the study. Prazosin (0.3 mumol/l) reduced contractions and the overflow of ATP elicited by both HNS and FS; the evoked overflow of tritium was not changed (210 pulses/7 Hz). Combined administration of prazosin (0.3 mumol/l) and suramin (300 mumol/l) abolished contractions and reduced the overflow of ATP elicited by both HNS and FS slightly more than did prazosin alone; tritium overflow again was not changed (210 pulses/7 Hz). Contractions, tritium overflow and ATP overflow increased with the frequency of both HNS and FS (from 7 to 25 Hz; 210 pulses); the increase in ATP overflow with frequency was more marked than the increase in tritium overflow. The preferential increase of ATP overflow with the frequency of HNS and FS persisted in the combined presence of prazosin (0.3 mumol/l) and suramin (300 mumol/l). The study confirms for HNS, a more physiologic way of sympathetic nerve stimulation, several observations previously obtained with FS. First, HNS-evoked ATP release is detectable as an overflow of ATP into the superfusion fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1983

The effect of decentralisation or chronic hypogastric nerve stimulation in vivo on the innervation and responses of the guinea-pig vas deferens.

The physiological, pharmacological and morphological characteristics of guinea-pig vas deferens supplied by hypogastric nerves rendered inactive by decentralisation were compared with those of vas deferens in which the nerve supply had been chronically stimulated for 3-9 days using implanted electrodes. No change was seen in decentralised preparations prior to 7 days, but from 8-15 days, increased sensitivity to application of noradrenaline in vitro was observed, which was shown to be related to reduced transmitter uptake by nerve terminals as well as to an increase in postjunctional sensitivity; there was also increased fatigability 7-14 days following decentralisation. Continuous stimulation of hypogastric nerves at 2 Hz for 4-8 h daily for 4-8 days resulted in enhanced transmitter uptake and reduced responses to noradrenaline; this was associated with a slight increase in noradrenaline content and a faster adrenergic neuromuscular response with a shorter latency. No appreciable changes in nerve or muscle structure studied by electron microscopy were observed following decentralisation, but there was an increase of between 12.5 and 29.6% in the number of close (less than 100 nm) neuromuscular junctions following chronic stimulation for 8 days.

Acetylcholine↗
PubMed1983

The long-term influence of decentralisation or preganglionic hypogastric nerve stimulation in vivo on the reinnervation of minced vas deferens in the guinea-pig.

Previous studies have shown that minced regenerating smooth muscle of the guinea-pig vas deferens becomes reinnervated by nerves growing in from the surrounding intact vas deferens. Using electron microscopy, we have examined the effect of altering activity in the preganglionic nerves, either by decentralisation, or by chronic stimulation of the hypogastric nerve, in vivo, on the reinnervation of regenerating smooth muscle cells. Chronic stimulation induced earlier reinnervation than that seen in unstimulated (sham-operated) or decentralised preparations; the number of nerve profiles present in four preparations stimulated for up to 7 days was approximately 10-20 times that seen in unstimulated or decentralised preparations. However, electron micrographs revealed that "empty" nerve terminals were a feature following stimulation for longer periods. Decentralised preparations showed little change of reinnervation, at least up to 7 weeks. Compensatory changes in the density of innervation were found in the unstimulated contralateral vas deferens.

Adrenergic Fibers↗
PubMed1979

Vacuolated neurons in the hypogastric ganglion of the rat.

The vacuolated neurons (VN) of the main hypogastric ganglion of the male rat were studied using the formaldehyde-induced fluorescence (FIF) method for the histochemical demonstration of catecholamines. Microspectrofluorimetry was performed to identify the fluorophores and to quantify the FIF. The thiocholine method (Koelle-Gomori) was used to demonstrate acetylcholinesterase activity. The fine structure of the VN was studied using glutaraldehyde/OsO4 fixation. (1) In the untreated adult male rat VN represent only a small population of the total number of hypogastric neurons (0.8--1.2%). The vacuoles are similar to those of the VN from the corresponding female ganglion. (2) The VN are considered to be adrenergic due to the nature of their fluorophore, indicating a primary catecholamine. (3) The first VN appear in the hypogastric ganglia at the age of 7 weeks. After testosterone administration to young rats, VN are found at the age of 4 weeks. (4) The basic fine structure of the VN is similar to that of other ordinary neurons of the hypogastric ganglia. (5) The content of the vacuoles could not be identified. (6) Indications of degeneration were not observed in the VN. (7) The VN are interpreted as being a functional stage of the "short" adrenergic neurons, which are under the control of steroid hormones. (8) Fifteen months after castration, no VN could be found in the hypogastric ganglia, while their number was normal in the corresponding control animals.

Acetylcholinesterase↗
PubMed1983

Axonal transport of noradrenaline, protein and glycoprotein in cat hypogastric nerves in vitro under conditions of high extracellular glucose.

Inferior mesenteric ganglia with attached hypogastric nerves were removed from anaesthetised cats and maintained in Eagle's Minimal Essential Medium in specially designed organ culture chambers for 48 h at 37 degrees C. The chambers had removable barriers so that the fluid bathing the ganglia was separated from that bathing the nerve trunks by inert silicone grease seals. (3H)-fucose (1.25 muCi/ml) and (14C)-leucine (0.5 muCi/ml) were added to the fluid bathing the ganglia at the start of the experiment. At this time, tight ligatures were applied to the hypogastric nerves so that the incorporated isotopes accumulated proximal to the constrictions due to interrupted axonal transport. The nerve trunks were bathed in medium containing glucose at either 5.5 or 25 mmol/l. At the end of the incubation period, the accumulations, proximal to the constrictions, of incorporated leucine and fucose and of noradrenaline were measured. The high glucose medium caused a 27.5% (p less than 0.001) reduction in the accumulation of fucose and a 19.2% (p less than 0.01) reduction in the accumulation of leucine. The incorporation of these tracers in the ganglia was unaffected by exposure of the nerve trunks to high glucose. The accumulation of noradrenaline proximal to the constrictions was also unaffected. Further experiments were performed to show that the reduced accumulations of fucose and leucine under conditions of high glucose were not due to loss of isotope from macromolecules in the axons nor to the small increase in osmotic pressure effected by addition of extra glucose to the culture medium. It is therefore suggested that elevation of extracellular glucose caused an impairment of axonal transport of incorporated leucine and fucose.

Animals↗
PubMed1981

An angiographic study of erection in the dog.

Erections were produced in dogs by stimulating the pudendal, the pelvic and the hypogastric nerves either singly or in combination and angiographic studies were then performed. During an erection an increase in blood flow to the erectile tissue could be demonstrated together with an impaired venous return.

Angiography↗
PubMed1994

Selective association of nerve fibres immunoreactive for substance P or bombesin with putative cholinergic neurons of the male rat major pelvic ganglion.

The male rat major pelvic ganglion contains both sympathetic and parasympathetic neurons that supply the lower urinary and digestive tracts, and the reproductive organs. The aim of this study was to describe the distribution and identify potential targets of sensory and intestinofugal axons in this ganglion. Two putative markers of these projections were chosen, substance P for primary sensory axons and bombesin for myenteric intestinofugal projections. Varicose substance P-immunoreactive axons were associated only with non-noradrenergic (putative cholinergic) somata, and most commonly with those that contained vasoactive intestinal peptide. Immunoreactivity for substance P was also present in a small group of non-noradrenergic somata, many of which were immunoreactive for enkephalins, neuropeptide Y or vasoactive intestinal peptide. Bombesin immunoreactivity was found only in preterminal and terminal (varicose) axons, the latter of which were exclusively associated with non-noradrenergic somata that contain neuropeptide Y-immunoreactivity. Some varicose axons containing either substance P- or bombesin-immunoreactivity were intermingled with clumps of small, intensely fluorescent cells. These studies indicate that substance P- and bombesin-immunoreactive axons are likely to connect with numerically small, but discrete, populations of pelvic neurons.

Adrenergic Fibers↗
PubMed1980

The effect of ageing on the SIF-cells in the hypogastric (main pelvic) ganglion of the rat.

The effect of ageing on SIF-cells was studied by the formaldehyde-induced fluorescence (FIF) method and by electron microscopy (EM). Microspectrofluorimetry was used to record emission spectra in FIF preparations. In newborn and in young adult (8--12 weeks) rats a single type of SIF-cell emitting greenish-yellow FIF was found while in aged rats a second type of SIF-cell emitting yellowish-brown granular FIF was also present. The intensity of the yellowish-brown FIF was lower than that of the greenish-yellow FIF. Also a few bright cytoplasmic fluorescent areas were occasionally found in some SIF-cells. The distribution of the SIF-cells through the ganglion did not change remarkably with age. In EM after glutaraldehyde-fixation in newborn and in young adult rats two types of small granule-containing (SGC) cells were distinguished according to the size of the dense cored vesicles, 1) 50--150 nm and 2) 50--250 nm. In aged rats, a third type of SGC-cells containing 50 x 250 nm elongated dense core vesicles could also be distinguished. After KMnO4-fixation in newborn and in young adult rats the classification was identical with glutaraldehyde-fixation. In aged rats three types of storage granules were found after KMnO4, 1) 100--300 nm empty vesicles and 2) 100--300 nm vesicles with small dense core, 3) 100--500 nm irregular in shape and filled with electron opaque material with a more dense core.

Aging↗