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B Conte

Publications and source records attributed to B Conte.

At least 37 records · Page 2Linked to original sources

Simultaneous recording of vesical and urethral pressure in urethane-anesthetized rats: effect of neuromuscular blocking agents on the activity of the external urethral sphincter.

In urethane-anesthetized rats we made a disconnection of the urinary bladder from the urethra and performed a simultaneous recording of the vesical and external urethral sphincter (EUS) pressures. Throughout the collecting phase, the EUS pressure was higher than that recorded into the bladder. Gallamine (10 mg/kg i.v.) or d-tubocurarine (100 micrograms/kg i.v.), did not alter the value of intraurethral pressure. When a reflex bladder contraction occurred in response to filling (expulsion phase) the intravesical pressure exceeded the urethral pressure and at the top of the vesical contraction a series of rapid intraluminal pressure high frequency oscillations (IPHFO) were recorded at the urethral recording site, which were abolished by neuromuscular blocking agents as well as after acute sectioning of pudendal nerves. IPHFO was still present in rats in which the periurethral muscles (pelvic floor), have been precedently dissected. To get further information about the physiological consequence of the EUS functional impairment induced by neuromuscular blocking agents, we used the non-stop transvesical cystometrogram. In these conditions, blockade of the EUS did not produce passive urine dripping during the filling phase, but absence of the rhythmic striated urethral activity during the vesical expulsion phase produced a significant increase of the residual volume from 35% (control) to 75%. We present an original pharmacological method in a species whose small dimensions create technical problems for recording pressure signals from the lower urinary tract. Moreover, we have gained information on the origin of the IPHFOs and about the role of the EUS during the collecting and the expulsion phase of the voiding cycle in urethane anesthetized rats.

Animals↗

Acrylamide-induced visceral neuropathy: evidence for the involvement of capsaicin-sensitive nerves of the rat urinary bladder.

The mechanisms underlying the severe urinary retention induced by acrylamide intoxication were studied in detail in the rat. Subcutaneous treatment with acrylamide monomer (50 mg/kg daily for 10 days) almost completely impaired the micturition reflex, resulting in urinary retention. In fact, the ability to eliminate an oral water load was virtually abolished, while bladder filling with saline (transvesical cystometrogram) failed to activate reflex micturition. Instead, a picture of overflow incontinence resulted in urethane-anaesthetized rats, which was not reversed by intravenous administration of 4-aminopyridine. The nerve-mediated contractile response to field stimulation (0.1-20 Hz, 0.5 ms, 60 V) of the isolated bladder was unaffected, thus suggesting the integrity of bladder efferent innervation, and no evidence was found from in vitro experiments that the myogenic contractility of the bladder was depressed by acrylamide treatment. Conversely, the sensory nerve-mediated response to capsaicin was abolished and sensory nerve fibres of the bladder were selectively depleted of their content of substance P- and calcitonin gene-related peptide immunoreactivity following acrylamide treatment. In fact, concentrations of the same neuropeptides in other organs, including the adjoining ureters, were unaffected. As to the urethral segment, including the striated sphincter, the D-tubocurarine (0.2 mM)-sensitive urethral response to electrical stimulation (0.1 Hz, 0.1 ms, 20 V) was significantly reduced in acrylamide-treated animals. At the same level, neurofilament protein immunostaining revealed striking accumulations of neurofilament protein-like material in motor end-plates, thus indicating that neuromuscular junctions of the urethral striated sphincter were severely affected. Thus, the afferent arm of the micturition reflex was shown to be severely deranged by acrylamide intoxication, especially in its capsaicin-sensitive component. Since twitch-like contractions of the urethral striated sphincter are probably involved in promoting bladder voiding, a decreased efficiency of this mechanism could participate in the picture of urinary retention induced by acrylamide.

Acrylamide↗

Mechanical irritation induces neurogenic inflammation in the rat urethra.

A catheter was inserted into the urethral meatus of urethane-anaesthetized rats and rotated (30 rotations/minute) during a three minute period. One hour later, microvascular permeability in the distal urethra was evaluated by means of the Evans Blue leakage technique. Dye extravasation increased significantly (74 +/- 12 ng./mg. of wet tissue weight, p less than 0.05), as compared to control values (18 +/- 2 ng./mg.). The effect of catheterism was prevented by about 50% by systemic pretreatment with capsaicin performed in either adult or newborn rats, as well as by bilateral removal of pelvic ganglia. Furthermore, pretreatment with capsaicin of adult rats, combined to pelvic ganglionectomy, virtually abolished the inflammatory response produced by mechanical irritation of the urethra. These results indicate that: 1) the increase of vascular permeability produced by mechanical irritation is nerve-mediated, 2) capsaicin-sensitive afferents participate in the inflammatory process and 3) capsaicin-insensitive nerves, which pass through the pelvic ganglia, contribute to the overall response.

Animals↗

Evidence for the existence of a urethro-urethral excitatory reflex in urethane anesthetized rats: involvement of peripheral ganglionic structures.

In urethane-anesthetized rats urethral distension with saline at the level of the external urethral sphincter elicited a series of slow phasic contractions with an amplitude between two and 18 mm. Hg. Contractions having an amplitude lower than four mm Hg were unaffected by i.v. or topical hexamethonium (HEX) or by topical tetrodotoxin (TTX). HEX or TTX transiently abolished or reduced the distension-evoked contractions having an amplitude between four and 18 mm. Hg. Administration of d-tubocurarine (d-Tc), atropine, bilateral section of pudendal nerves, spinalization (T12-S1) or bilateral removal of the major pelvic ganglia did not modify the distension-induced rhythmic urethral activity. In rats desensitized to capsaicin (four days before), both amplitude and frequency of urethral contractions did not differ from control value. In rats pretreated with atropine, administration of HEX still inhibited the distension-induced urethral contractions. Intravenous dimethylphenylpiperazinium (DMPP) triggered a rapid phasic contraction with an amplitude ranging between 15 and 25 mm. Hg. This effect was inhibited by previous administration of HEX. In accordance with histochemical studies showing spherical ganglionic cell bodies between the outermost striated muscle layer and the smooth muscular coat, present data indicate that distension of the external urethral sphincter reflexly activates urethral contractions, possibly through a local mechanism.

Anesthesia↗

Involvement of capsaicin-sensitive nerves of the rat urinary bladder in acrylamide neuropathy.

Acrylamide monomer is neurotoxic in man and experimental animals, producing a sensorimotor distal axonopathy. In spite of remarkable effect of acrylamide on micturition, resulting in urine retention in both man and rat, bladder autonomic innervation has been little studied. This study focused on the effect of acrylamide on capsaicin-sensitive nerves of the rat bladder, because of the role played by these fibres in regulating the afferent arm of reflex micturition.

Acrylamide↗

Effect of urethane anesthesia on the micturition reflex in capsaicin-treated rats.

Cystometry was performed on rats with a chronically implanted intravesical catheter (2 days before cystometry) before and after induction of urethane-anesthesia. Four groups of animals were investigated: group A, vehicle-treated; group B, capsaicin-treated as adults (50 mg/kg s.c.) 4 days before cystometry; group C, capsaicin-treated as adults (125 mg/kg s.c.) 4 days before cystometry; and group D, capsaicin-treated as newborns (50 mg/kg) 2 months before. Rats of group D had a markedly enlarged bladder. Before induction of urethane anesthesia, the bladder capacity of rats of groups A, B and C was not significantly different from each other, while that of rats of group D was larger than controls. After induction of anesthesia bladder capacity in groups B and C was significantly increased as compared to group A and micturition was abolished in group D (overflow incontinence). Amplitude of micturition contraction was significantly reduced in all groups after induction of anesthesia but was unaffected by capsaicin pretreatment. It is concluded that the facilitatory action of capsaicin-sensitive nerves on micturition threshold is more evident in anesthetized than awake rats and that capsaicin-resistant bladder afferents are more sensitive to the depressant action of urethane than the capsaicin-sensitive ones.

Anesthesia↗

The contractile effect of tachykinins on human prostatic urethra: involvement of NK-2 receptors.

The contractile response to natural tachykinins [substance P (SP), neurokinin A (NKA), arginin-neurokinin B (ArgNKB)] and to synthetic peptide [Pro9]SP sulfone, [beta Ala8]NKA(4-10) and [MePhe7]NKB, were investigated in the isolated smooth muscle from the human prostatic urethra. Natural tachykinins evoked concentration-related responses with the following order of potency: NKA----NKB--------SP. Among selective agonists [beta Ala8]NKA(4-10) produced concentration-related contractions, while [Pro9]SP sulfone and [MePhe7]NKB were inactive. These data indicate the presence of NK-2 receptors in the smooth muscle of the human prostatic urethra.

Aged↗

[A pharmacological and clinical review on the activity of a bovine factor VIII derivative obtained by enzymatic hydrolysis].

We report pharmacological, experimental and clinical data of the new drug which decreases bleeding time but is devoid of procoagulant and platelet aggregating properties. The drug, derived from bovine factor VIII by enzymatic hydrolysis, did not show toxicological and immunological effects either in animals or in patients. In addition we report the review of the clinical studies in different pathological situations i.e. ophthalmology, odontostomatology, gynecology etc.

Adult↗

Opioid-like action of eseroline on micturition reflex in rats.

1. Eseroline (3-10 mg/kg s.c.), the first product of metabolic breakdown of eserine (physostigmine) markedly increased bladder capacity and decreased voiding efficiency of reflex micturition in rats. 2. Eserine had an opposite effect on bladder function in vivo, while morphine (1-3 mg/kg s.c.) reproduced the action of eseroline. The effects of eseroline or morphine were prevented by naloxone which per se reduced bladder capacity. 3. In vitro both eserine and eseroline potentiated the cholinergic component of the twitch response to field stimulation of the rat bladder and this effect was atropine-sensitive while morphine had no effect. 4. These findings provide further support to the notion that eseroline possesses both eserine- and opioid-like actions, but this latter predominates in determining its actions on bladder function in vivo.

Acetylcholine↗

Further studies on mechanisms regulating the voiding cycle of the rat urinary bladder.

1. The effect of transection of pudendal or hypogastric nerves and of various pharmacological pretreatments on the bladder voiding cycle elicited by saline filling was investigated in urethane-anesthetized rats. 2. Sectioning of pudendal nerves reduced efficiency of the expulsive phase of the voiding cycle while sectioning of hypogastric nerves enhanced voiding efficiency and reduced residual volume. 3. An increased voiding efficiency was also observed in 6-hydroxydopamine-treated rats. 4. Atropine and physostigmine decreased and increased voiding efficiency, respectively. Indomethacin pretreatment produced a marked increase in residual volume. 5. These findings indicate that the autonomic innervation of the bladder and urethra as well as production of local factors such as prostanoids regulates not only the collecting phase of the cystometragram but also influence markedly voiding efficiency.

Animals↗

A method for studying pain arising from the urinary bladder in conscious, freely-moving rats.

A new technique has been developed suitable for quantitative studies on physio-pharmacology of pain arising from the urinary bladder in conscious freely-moving rats. The method involves the intravesical instillation of xylene or its vehicle (0.3 cc of silicone oil) through a catheter chronically implanted into the rat bladder. The instillation of xylene (10 to 100%) produced behavioural effects (licking of lower abdomen or perineal region, hind paws hyperextension) suggestive of visceral pain. All the behavioural responses produced by xylene instillation were prevented by extrinsic bladder denervation (pelvic ganglionectomy). Morphine HCl (two to five mg./kg. s.c., 30 min. before) or (+/-)-baclofen (2.5-10 mg./kg. s.c., 60 min. before) reduced or abolished the response to xylene instillation, thus indicating that the action of analgesic drugs can be quantitated using the present model.

Animals↗

Effects of tachykinins and selective tachykinin receptor agonists on vascular permeability in the rat lower urinary tract: evidence for the involvement of NK-1 receptors.

1. Intravenous administration of three mammalian tachykinins (substance P, neurokinin A and neurokinin B) and three non-mammalian tachykinins (physalaemin, eledoisin and kassinin) induced dose-dependent increases in vascular permeability, as measured by Evans blue leakage technique, in various segments of the lower urinary tract (bladder dome and neck, proximal urethra, ureters) in urethane-anaesthetized rats. 2. Plasma extravasation induced by substance P (3.71 nmol kg-1 i.v.) was unaffected by pretreatment with antihistaminic drugs or methysergide. 3. A comparison of the relative potencies of various tachykinins did not allow characterization of a distinct type of receptor involved in the increase in vascular permeability. 4. The effects of tachykinin-related peptides which are selective agonists at the NK-1 (substance P-methylester, [Pro9]-SP-sulphone), NK-2 receptor [( Nle10]-NKA(4-10] or NK-3 receptor [( MePhe7]-NKB(4-10) and Senktide) indicated that NK-1 agonists are effective in the whole lower urinary tract, while NK-2 or NK-3 agonists are inactive or weakly active. 5. [beta-Ala4, Sar9]-SP(4-11)-sulphone, a selective NK-1 receptor agonist devoid of histamine-releasing properties, was highly potent and effective in producing plasma extravasation in the rat lower urinary tract. 6. These findings indicate that NK-1 receptors mediate the effect of intravenous tachykinins on vascular permeability in the rat lower urinary tract, through a histamine-independent mechanism.

Animals↗

The effect of SC-19220, a prostaglandin antagonist, on the micturition reflex in rats.

SC-19220 (5-20 mg/kg i.v.), a competitive receptor antagonist of PGE, increased the bladder capacity and reduced the voiding efficiency of micturition (elicited by slow transvesical filling) of urethane-anesthetized rats. The effect of SC-19220 was prevented by indomethacin pretreatment, whereas indomethacin per se mimicked the effects of SC-19220. SC-19220 produced a competitive rightward shift of the dose-response curve for the contractile effect induced by PGE2 on strips of rat detrusor muscle in vitro, whereas the amplitude of nerve-mediated twitches was unaffected. These findings support the hypothesis that endogenous PGE2 is physiologically involved in the regulation of vesicourethral motility in this species by facilitating attainment of the micturition threshold during the collection phase of the cystometrogram.

Animals↗

The effect of 4-aminopyridine on micturition reflex in normal or capsaicin-desensitized rats.

4-aminopyridine (4-AP) produced a dose-related (0.15-2 mg/kg i.v.) potentiation of the voiding cycle of the urinary bladder and increased frequency of micturition in urethane-anesthetized rats. In bladders containing a subthreshold amount of fluid for eliciting reflex micturition 4-AP (1-3 mg/kg i.v.) activated a series of high-amplitude, hexamethonium-sensitive rhythmic bladder contractions. In rats desensitized to capsaicin as newborns, reflex micturition was almost abolished: in these animals i.v. 4-AP did not affect bladder voiding unless at high doses (1-2 mg/kg), at which a reversal from anesthesia occurred. This was accompanied by a prompt micturition. In unanesthetized rats, neither the 4-AP-induced convulsions nor the behavioral response (assessed in an open field) to 4-AP were affected by neonatal capsaicin desensitization. Daily urine production of capsaicin-pretreated animals did not differ from that of controls. However, when measurements were made during daytime, almost no spontaneous urine emission was found in capsaicin-treated rats. On the rat isolated urinary bladder, 4-AP potentiated the response to field stimulation in preparations from both vehicle- and capsaicin-pretreated animals. These findings indicate that 4-AP has a potent excitatory action on bladder voiding in rats and support the hypothesis that in this species 'conscious' bladder voiding can be initiated through capsaicin-resistant mechanisms.

4-Aminopyridine↗

Prostanoids modulate reflex micturition by acting through capsaicin-sensitive afferents.

Topical application of exogenous prostanoids (PGE2, TBX B2) on the serosal surface of the urinary bladder of urethane-anaesthetized rats activated reflex micturition. Likewise, intravesical instillation of PGE2 during the cystometrogram lowered the threshold for reflex micturition. Both effects were prevented by systemic capsaicin desensitization (50 mg/kg s.c., 4 days before). Indomethacin pretreatment and systemic capsaicin desensitization each increased the micturition threshold without affecting the amplitude of micturition contraction. However, the effect of the two treatments combined was not greater than the effect of either alone. These findings support the idea that endogenous prostanoids facilitate reflex micturition by stimulating or sensitizing, directly or indirectly, the subset of bladder mechanoreceptors which is capsaicin-sensitive in adult rats.

Animals↗

The contribution of capsaicin-sensitive sensory nerves to xylene-induced visceral pain in conscious, freely moving rats.

1. Intravesical instillation of xylene (10-100%, dissolved in silicone oil) through a catheter implanted into the bladder of conscious, freely-moving rats produced behavioural effects (licking of lower abdomen or perineal region) suggestive of intense visceral pain, not mimicked by topical application of the irritant on the urethral outlet. 2. The xylene-induced visceral pain was prevented, to the same extent, by systemic desensitization to capsaicin (50 mg/kg s.c.) performed in either adult or newborn rats, as well as by extrinsic bladder denervation (pelvic ganglionectomy), thus indicating the involvement of primary afferents in the bladder wall. 3. Other behavioural responses induced by xylene instillation into the bladder (hind limb hyperextension, grooming) were not affected by systemic capsaicin desensitization in either adult or newborn rats, but were abolished by bladder denervation. 4. Systemic capsaicin desensitization produced an almost complete depletion of substance P-, neurokinin A-like and calcitonin gene-related peptide-like immunoreactivity in the rat urinary bladder. 5. These findings indicate that, in addition to their role in activating reflex micturition, the neuropeptides-containing capsaicin-sensitive sensory nerves of the rat bladder are involved in chemogenic visceral pain.

Aging↗

New method for recording cystometrograms in conscious, freely moving rats.

A new cystometric technique has been developed that is suitable for quantitative studies on physiopharmacology of micturition in conscious, freely moving rats. The method involves the transvesical infusion of warm saline at various filling rates through a catheter chronically implanted into the bladder dome. The various parameters of the collecting and voiding phase of the cystometrogram were recorded. Results obtained indicate that characteristics of the bladder voiding cycle of conscious, freely moving rats are qualitatively similar but quantitatively different from those described previously in anesthetized animals.

Animals↗